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Biomedical subjects

M Trujillo

Publications and source records attributed to M Trujillo.

At least 19 recordsLinked to original sources

Factors influencing the anti-inflammatory effect of dexamethasone therapy in experimental pneumococcal meningitis.

Dexamethasone (DXM) interferes with the production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) and can thereby diminish the secondary inflammatory response that follows initiation of antibacterial therapy. A beneficial effect on the outcome of Haemophilus meningitis in children has been proven, but until recently the effect of DXM therapy in pneumococcal meningitis was uncertain. The aim of the present study was to evaluate factors that might influence the modulatory effect of DXM on the antibiotic-induced inflammatory response in a rabbit model of pneumococcal meningitis. DXM (1 mg/kg) was given intravenously 30 min before or 1 h after administration of a pneumococcal cell wall extract, or the first dose of ampicillin. In meningitis induced by cell wall extract, DXM therapy prevented the increase in cerebrospinal fluid (CSF) leucocyte and lactate concentrations, but only if given 30 min before the cell wall extract. In meningitis caused by live organisms, initiation of ampicillin therapy resulted in an increase in CSF TNF-alpha and lactate concentrations only in animals with initial CSF bacterial concentrations > or =5.6 log10 cfu/mL. In those animals, DXM therapy prevented significant elevations in CSF TNF-alpha [median change -184 pg/mL, -114 pg/mL versus +683 pg/mL with DXM (30 min before or 1 h after ampicillin) versus controls (no DXM), respectively, P=0.02] and lactate concentrations [median change -10.6 mmol/L, -1.5 mmol/L versus +14.3 mmol/L with DXM (30 min before or 1 h after ampicillin) versus controls (no DXM), respectively, P=0.01]. These effects were independent of the timing of DXM administration. In this model of experimental pneumococcal meningitis, an antibiotic-induced secondary inflammatory response in the CSF was demonstrated only in animals with high initial CSF bacterial concentrations (> or =5.6 log10 cfu/mL). These effects were modulated by DXM therapy whether it was given 30 min before or 1 h after the first dose of ampicillin.

Animals↗

Congenital dyserthropoietic anaemia other than type I to III with a peculiar erythroblastic morphology.

Here, we report the case of a child who, since birth, showed persistent macrocytosis and elevated mean corpuscular volume of the erythrocytes. Bone marrow biopsy revealed gross disorganisation of the erythroblastic series both at the light and electron microscopic examination, with complete absence of dysplastic features in the granulocytic and megakaryocytic series. Common causes of macrocytosis were excluded. The spectrum of morphological findings were not consistent with any of the classical types of congenital dyserythropoietic anaemias (CDAs) and serological findings of CDA type II were absent. The most outstanding feature was a marked irregularity of the nuclear outline of the late erythroblasts that presented thick-ending finger-like projections. The combination of macrocytosis without anaemia and these morphologic erythroblastic changes have not been previously reported in the setting of classical and variant forms of CDAs.

Anemia, Dyserythropoietic, Congenital↗

Step-by-step uncoordination of the pyrazolyl rings of hydrotris(pyrazolyl)borate ligands in comlexes of Rh and RhIII.

Compounds of rhodium(I) and rhodium(III) that contain ancillary hydrotris(pyrazolyl)borate ligands (Tp') react with monodentate and bidentate tertiary phosphanes in a step-wise manner, with incorporation of P-donor atoms and concomitant replacement of the Tp' pyrazolyl rings. Accordingly, [Rh(kappa3-TpMe2)(C2H4)(PMe3)] (1b), converts initially into [Rh(kappa2-TpMe2)-(PMe3)2] (3), and then into [Rh(kappa1-TpMe2)-(PMe3)3] (2) upon interaction with PMe3 at room temperature, in a process which can be readily reversed under appropriate experimental conditions. Full disengagement of the Tp' ligand is feasible to give Tp' salts of rhodium(I) complex cations, for example, [Rh(CO)(dppp)2]-[TpMe2,4-Cl] (5; dppp = Ph2P(CH2)3PPh2), or [Rh(dppp)2][TpMe2,4-Cl] (6). Bis(hydride) derivatives of rhodium(III) exhibit similar substitution chemistry, for instance, the neutral complex [Rh(Tp)-(H)2(PMe3)] reacts at 20 degrees C with an excess of PMe3 to give [Rh(H)2-(PMe3)4][Tp] (9b). Single-crystal X-ray studies of 9b, conducted at 143 K, demonstrate the absence of bonding interactions between the [Rh(H)2(PMe3)4]+ and Tp ions, the closest Rh...N contact being at 4.627 A.

Journal Article↗

Identification of novel RP2 mutations in a subset of X-linked retinitis pigmentosa families and prediction of new domains.

X-linked Retinitis Pigmentosa (XLRP) shows a huge genetic heterogeneity with almost five distinct loci on the X chromosome. So far, only two XLRP genes have been identified, RPGR (or RP3) and RP2, being mutated in approximately 70% and 10% of the XLRP patients. Clinically there is no clearly significative difference between RP3 and RP2 phenotypes. In the attempt to assess the degree of involvement of the RP2 gene, we performed a complete mutation analysis in a cohort of patients and we identified five novel mutations in five different XLRP families. These mutations include three missense mutations, a splice site mutation, and a single base insertion, which, because of frameshift, anticipates a stop codon. Four mutations fall in RP2 exon 2 and one in exon 3. Evidence that such mutations are different from the 21 RP2 mutations described thus far suggests that a high mutation rate occurs at the RP2 locus, and that most mutations arise independently, without a founder effect. Our mutation analysis confirms the percentage of RP2 mutations detected so far in populations of different ethnic origin. In addition to novel mutations, we report here that a deeper sequence analysis of the RP2 product predicts, in addition to cofactor C homology domain, further putative functional domains, and that some novel mutations identify RP2 amino acid residues which are evolutionary conserved, hence possibly crucial to the RP2 function.

Amino Acid Sequence↗

Culture and the organization of psychiatric care.

Health care systems of the 21st century confront the confluence of two important forces that conform their policies regarding culture. On the one hand, population demographics announce increasing diversity; on the other, a rising knowledge base regarding the impact of culture on mental health awaits to be incorporated into actual clinical practices nationwide. As regulators and payors incorporate this knowledge into their practices, standards and guidelines, the dream of mental health cultural parity will come somewhat closer to fulfillment. In this article, we have aimed to review how the integration of developing knowledge and evolving standards may contribute to such fulfillment.

Cross-Cultural Comparison↗

Determination of phenols, flavones, and lignans in virgin olive oils by solid-phase extraction and high-performance liquid chromatography with diode array ultraviolet detection.

A simple analytical method for the quantitative determination of phenols, flavones, and lignans in virgin olive oils was developed. The polar fraction was isolated from small amounts of oil sample (2.5 g) by solid-phase extraction (SPE) using diol-phase cartridges, and the extract was analyzed by reversed-phase HPLC coupled with diode array UV detection. Chromatographic separation of pinoresinol, cinnamic acid, and 1-acetoxypinoresinol was achieved. Repeatability (RSD < 6.5%), recovery (> 90%), and response factors for each identified component were determined. SPE on amino-phase cartridges was used for isolating acidic phenols and as an aid for phenol identification. For the first time, 2-(4-hydroxyphenyl)ethyl acetate was detected in olive oils. The aldehydic structure of the ligstroside aglycon was confirmed by NMR spectroscopy. The colorimetric determination of total o-diphenolic compounds by reaction with molybdate was consistent with their HPLC determination. Differences between results obtained by liquid-liquid extraction and SPE were not statistically significant.

Chromatography, High Pressure Liquid↗

Differential expression of putative cell death regulator genes in near-isogenic, resistant and susceptible barley lines during interaction with the powdery mildew fungus.

We analysed pathogenesis-related expression of genes, that are assumed to be involved in ubiquitous plant defence mechanisms like the oxidative burst, the hypersensitive cell death reaction (HR) and formation of localized cell wall appositions (papillae). We carried out comparative northern blot and RT-PCR studies with near-isogenic barley (Hordeum vulgareL. cv. Pallas) lines (NILs) resistant or susceptible to the powdery mildew fungus race A6 (Blumeria graminis f.sp. hordei, BghA6). The NILs carrying one of the R-genes Mla12, Mlg or the mlo mutant allele mlo5 arrest fungal development by cell wall appositions (mlo5) or a HR (Mla12) or both (Mlg). Expression of an aspartate protease gene, an ascorbate peroxidase gene and a newly identified cysteine protease gene was up-regulated after inoculation with BghA6, whereas the constitutive expression-level of a BAS gene, that encodes an alkyl hydroperoxide reductase, was reduced. Expression of a newly identified barley homologue of a mammalian cell death regulator, Bax inhibitor 1, was enhanced after powdery mildew inoculation. An oxalate oxidase-like protein was stronger expressed in NILS expressing penetration resistance. A so far unknown gene that putatively encodes the large subunit of a superoxide generating NADPH oxidases was constitutively expressed in barley leaves and its expression pattern did not change after inoculation. A newly identified barley Rac1 homologue was expressed constitutively, such as the functionally linked NADPH oxidase gene. Gene expression patterns are discussed with regard to defence mechanisms and signal transduction.

Apoptosis↗

Synthesis, isolation and characterization of Plasmodium falciparum antigenic tetrabranched peptide dendrimers obtained by thiazolidine linkages.

Different chemical alternatives were evaluated for obtaining immunogenic polypeptidic macromolecules which could then be used as vaccines. These were based on the ligation reaction between an unprotected immunogenic peptide and an unprotected multifunctional core peptide; polyantigens, designated dendrimers because their form resembles that of dendritic cells, were thus obtained. The antigen-core ligation alternatives, studied by indirect synthesis, were the formation of oxime, hydrazone and thiazolidine linkages, making use of the reaction between a weak base (acting as nucleophile) and an alkyl aldehyde. The other alternative was the formation of a thioether linkage between a sulfydryl and an alkyl halide. Finally, a multiple antigen peptide (MAP) was synthesized by direct synthesis. All reactions were monitored by SEC-HPLC and SDS-PAGE. Dendrimer molecular mass obtained was confirmed by MS MALDI-TOF. Dendrimer purification was first carried out by concentrating crude reaction products with CP-5000 centricons and (using SEC-HPLC) pure tetramers were then obtained. A 20-residue 9376 immunogenic sequence, from Plasmodium falciparum apical merozoite antigen protein (AMA-1), was used to study the best alternative for chemical ligation. It was observed that thiazolidine formation proceeded with greater yield and in less time than the others. A tetramer has been simultaneously synthesized via thiazolidine with the SPf-66 antimalarial vaccine 45-residue monomer, proving the technique's versatility. The 9376 peptide disulfide bound polymer and SPf-66 (as well as their tetrameric thiazolidine dendrimers) were inoculated in rabbits to evaluate their antibody response. It was observed that titers for tetrameric thiazolidine dendrimers were not just greater but were also sustained over time. Western blot for pre-immune and immune sera showed that dendrimer sera recognized specific Plasmodium falciparum proteins as well as disulfide-bound polymers.

Aldehydes↗

Haloperidol blood levels in acute mania with psychosis.

In this study, the authors examined the relationship between steady-state haloperidol blood levels and clinical response in patients with acute psychotic mania. Fifty-four inpatients with acute mania were randomly assigned to receive either haloperidol 25 mg/day or haloperidol 5 mg/day. Each subject also received a concomitant medication: lorazepam 4 mg/day, lithium, or placebo. The relationship between steady-state haloperidol blood levels and clinical improvement was studied using analysis of covariance. There was wide interindividual variation in the haloperidol blood level-dose ratio. Haloperidol blood levels (log-transformed) were found to significantly correlate with clinical response in acute mania. Low-dose haloperidol with concomitant lithium may produce an optimal response in acute mania. Haloperidol blood levels may be clinically useful in identifying patients who are nonresponsive because of low drug levels and, hence, in enhancing optimal haloperidol dosing for acute mania with psychosis.

Adult↗

ATP synthase is necessary for microcin H47 antibiotic action.

Microcin H47 is a gene-encoded peptide antibiotic produced by a natural Escherichia coli strain isolated in Uruguay. In order to identify cellular components necessary for its antibiotic action, microcin H47-resistant mutants isolated in this work, as well as previously described mutants affected in membrane proteins, were analyzed. These studies indicated that (i) receptor outer membrane proteins for ferric-catechol siderophores would be involved in microcin-specific binding to the cell surface, (ii) the TonB pathway is needed for microcin H47 uptake, and (iii) the presence of the ATP synthase complex is necessary for microcin action. The possibility that this last structure contains the antibiotic target is discussed.

Adenosine Triphosphatases↗

Hormonal regulation of the contractile response induced by okadaic acid in the rat uterus.

The contractile effect of okadaic acid (OA), a highly selective inhibitor of protein serine/threonine phosphatases, was analyzed in the rat uterus during the estrous cycle and during the course of pregnancy. Contractile effects were related to circulating levels of estrogen and progesterone and to mRNA levels of myosin light chain kinase (MLCK) and of myosin light chain protein phosphatase catalytic (PP1-delta) and larger regulatory subunit (MYPT). Both in nonpregnant and pregnant uteri, OA (20 microM) induced a transient contraction, which after plateauing, slowly decreased. In the nonpregnant uterus, the amplitude of this contraction varied at different stages of the estrous cycle, being higher at proestrus and lower at diestrus. In the pregnant uterus, the contraction to OA increased significantly during the course of pregnancy, reaching a maximum in day 21 pregnant rats, and declined after delivery. Whatever the day of pregnancy, the amplitude of the contraction to OA was not significantly modified when obtained in Ca(2+)-free solution. The magnitude of the OA-induced contraction in spontaneously cycling and pregnant rats was positively correlated to the ratio of estrogen/progesterone serum levels. Reverse transcription-polymerase chain reaction assays on myometrial tissue demonstrated that mRNA expression of PP1-delta and MYPT was higher at early (day 3) than at late (day 21) pregnancy. MLCK mRNA levels were similar in day 3 and day 21 pregnant rats. These data suggest that changes in the expression and activity of myosin phosphatase may contribute to modulating the level of uterine contractile force during the estrous cycle, pregnancy, and labor.

Animals↗

Amino terminal peptides of the ring infected erythrocyte surface antigen of Plasmodium falciparum bind specifically to erythrocytes.

The Ring-Infected Erythrocyte Surface Antigen (Pf155/RESA) sequence was chemically synthesized in fifty four 20-mer sequential peptides, covering the entire protein, each of which was tested in erythrocyte binding assays. Peptides 6671 and 6673, corresponding to residues 141-160 and 181-200, respectively, presented a high specific binding activity to erythrocytes with affinity constants of 190 nM and 105 nM respectively. Their binding was sensitive to previous enzymatic treatment of erythrocytes. A region of peptide 6673 has been identified, very recently, as a B-cell epitope, target of neutralizing antibodies (Siddique AB, Iqbal J, Ahlborg N, Wâhlin FB, Perlmann P, Berzins K. Antibodies to nonrepeat sequences of antigen Pf155/RESA of Plasmodium falciparum inhibit parasite growth in vitro. Parasitol Res 1998;84:485-91). The critical residues for erythrocyte binding for peptide 6671 (MTDVNRYRYSNNYEAIPHIS) and for peptide 6673 (LGRSGGDIIKKMQTLWDEIM) were recognized. Based on these data, the presence of five functional regions of RESA is postulated.

Amino Acid Sequence↗

Substitution and hydrogenation reactions on rhodium(I)-ethylene complexes of the hydrotris(pyrazolyl)borate ligands T (T = Tp, TpMe2).

The bis(ethylene) Rh species TpMe2Rh(C2H4)2(1*) (TpMe2 = tris(3,5-dimethyl-1-pyrazol-1-yl)hydroborate) has been obtained from [RhCl(C2H4)2]2 and KTpMe2. Complex 1* easily decomposes in solution to give mainly the butadiene species TpMe2Rh(eta74-C4H6). In the solid state its thermal decomposition follows a different course and the allyl TpMe2RhH(syn-C3H4Me) is cleanly obtained as a mixture of exo and endo isomers. The complexes Tp'Rh(C2H4)2 (Tp' = Tp, TpMe2) afford the monosubstituted species Tp'Rh(C2H4)(PR3) upon reaction with PR3 but react differently with L = CO or CNR: the Tp compound gives dinuclear [TpRh]2(mu-L)3 complexes, while, in the case of 1*, TpMe2Rh(C2H4)(L) species are obtained. The ethylene ligand of complexes TpMe2Rh(C2H4)(PR3) is labile, and several peroxo compounds of composition TpMe2Rh(O2)(PR3) have been isolated by their reaction with O2. All the mononuclear Rh(I) complexes are formulated as 18e- trigonal bipyramidal species on the basis of IR and NMR spectroscopic studies. A series of dihydride complexes of Rh(III) of formulation Tp'RhH2(PR3) have been prepared by the hydrogenation of the corresponding ethylene derivatives. Complexes [TpRh]2(mu-CNCy)3, TpMe2Rh(C2H4)(PEt3), and TpMe2Rh(O2)(PEt3) have been further characterized by X-ray diffraction studies.

Journal Article↗

Denticity Changes of Hydrotris(pyrazolyl)borate Ligands in Rh(I) and Rh(III) Compounds: From kappa(3)- to Ionic "kappa(0)"-Tp'

Isolated hydrotris(pyrazolyl)borate anions Tp' were obtained as salts of metal complex cations (see picture) by the displacement of Rh-coordinated kappa(3)-N,N',N"-Tp' by PMe(3) (Tp'=Tp and Tp(Me2)). With [(kappa(3)-Tp(Me2))Rh(C(2)H(4))(2)], stepwise diplacement of the Tp(Me2) ligand allowed the isolation of complexes exhibiting the kappa(2)- Tp(Me2) and kappa(1)-Tp(Me2) coordination modes.

Journal Article↗

Barley Mla and Rar mutants compromised in the hypersensitive cell death response against Blumeria graminis f.sp. hordei are modified in their ability to accumulate reactive oxygen intermediates at sites of fungal invasion.

The pathogenesis-related accumulation of superoxide radical anions (O2*-) and hydrogen peroxide (H2O2) was comparatively analyzed in a barley line (Hordeum vulgare L. cv Sultan-5) carrying the powdery mildew (Blumeria graminis f.sp. hordei, Speer, Bgh) resistance gene Mla12, and in susceptible mutants defective in Mla12 or in genes "required for Mla12-specified disease resistance" (Rar1 and Rar2). In-situ localization of reactive oxygen intermediates was performed both by microscopic detection of azide-insensitive nitroblue tetrazolium (NBT) reduction or diaminobenzidine (DAB) polymerization, and by an NBT-DAB double-staining procedure. The Mla12-mediated hypersensitive cell death occurred either in attacked epidermal cells or adjacent mesophyll cells of wild-type plants. Whole-cell H2O2 accumulation was detected in dying cells, while O2*- emerged in adjacent cells. Importantly, all susceptible mutants lacked these reactions. An oxalate oxidase, which is known to generate H2O2 and has been implicated in barley resistance against the powdery mildew fungus, was not differentially expressed between the wild type and all mutants. The results demonstrate that the Rar1 and Rar2 gene products, which are control elements of R-gene-mediated programmed cell death, also control accumulation of reactive oxygen intermediates but not the pathogenesis-related expression of oxalate oxidase.

Ascomycota↗

Treatment of catheter-induced thrombotic superior vena cava syndrome: a single institution's experience.

Thrombosis is the most frequent benign etiology of superior vena cava syndrome among cancer patients who have a long-term central venous catheter. In this paper, six cases of thrombotic superior vena cava syndrome are discussed. There were four women and two men. One patient was treated with streptokinase and five with urokinase. The mean age was 46 years (range 22-69), and the mean time for thrombosis development after catheter insertion was 125 days (range: 53-211 days). The mean time for resolution of thrombosis was 7 days (range 2-11) in five patients. One patient had no response to fibrinolysis.

Adult↗