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Biomedical subjects

A Arrieta

Publications and source records attributed to A Arrieta.

At least 19 recordsLinked to original sources
PubMed2001

On the mechanism of conversion of N-acyl-4-acyloxy-beta-lactams into 2-substituted 1,3-oxazin-6-ones. Can a low-barrier transition state be antiaromatic?

The mechanism of the conversion of N-acyl-4-acyloxy-beta-lactams into 1,3-oxazin-6-ones has been investigated using ab initio and density functional theories. It has been found that two pseudopericyclic reactions are involved in the whole process. The first key reaction is a retro-[4-exo-dig] cyclization instead of a thermal conrotatory electrocyclic ring opening. Magnetic characterization of the corresponding transition structure shows antiaromatic character, despite the low activation energy associated with this process. The second step is very exothermic and has no activation barrier. It corresponds to another pseudopericyclic reaction instead of a six-electron disrotatory electrocyclization. These results confirm that there is no correlation between aromaticity and pseudopericyclic reactions. In contrast, thermal-symmetry-allowed pericyclic reactions are always aromatic. Therefore, magnetic analysis of the corresponding transition structures constitutes a useful tool to distinguish between both kinds of processes.

Journal Article↗
PubMed2001

Empiric use of cefepime in the treatment of lower respiratory tract infections in children.

BACKGROUND: These studies were designed to assess the efficacy and safety of cefepime, a fourth generation cephalosporin, for the treatment of serious infections, including lower respiratory tract infections (LRTI) in children. METHODS: Four clinical trials of cefepime for the treatment of serious bacterial infections enrolled 259 children with LRTI. In 3 trials cefepime was compared with ceftazidime (n = 166), cefotaxime (n = 16) or cefuroxime (n = 12). One trial was noncomparative (n = 65). RESULTS: Treatment with cefepime 50 mg/kg/ dose administered every 8 to 12 h produced a satisfactory clinical response (clinical signs of infection resolved or improved with no evidence of recurrent infection at posttreatment follow-up) in 88 to 100% of patients, comparable with comparator therapy. In children from whom a causative pathogen was identified, bacteriologic eradication was comparable between cefepime and comparator therapy. Cefepime was as safe and well-tolerated as comparator therapy. Few treatment-related clinical or laboratory adverse events were noted and were equivalent to comparator in all studies. CONCLUSION: Cefepime is as effective, safe and well-tolerated for the empiric treatment of children with LRTI as comparator agents but offers the advantage of an enhanced spectrum of activity for Gram-positive and Gram-negative pathogens compared with second or third generation cephalosporins.

Adolescent↗
PubMed2001

Cytokine profiles of pediatric patients treated with antibiotics for pyelonephritis: potential therapeutic impact.

Urinary tract infections are common in infants and children. Pyelonephritis may result in serious complications, such as renal scarring, hypertension, and renal failure. Identification of the timing of release of inflammatory cytokines in relation to pyelonephritis and its treatment is essential for designing interventions that would minimize tissue damage. To this end, we measured urinary cytokine concentrations of interleukin-1 beta (IL-1 beta), IL-6, and IL-8 in infants and children with pyelonephritis and in healthy children. Children that presented to our institution with presumed urinary tract infection were given the diagnosis of pyelonephritis if they had a positive urine culture, pyuria, and one or more of the following indicators of systemic involvement: fever, elevated peripheral white blood cell count, or elevated C-reactive protein. Urine samples were obtained at the time of presentation prior to the administration of antibiotics, immediately after completion of the first dose of antibiotics, and at follow up 12 to 24 h after presentation. IL-1 beta, IL-6, and IL-8 concentrations were measured by enzyme-linked immunosorbent assay. Creatinine concentrations were also determined, and cytokine/creatinine ratios were calculated to standardize samples. Differences between pre-antibiotic and follow-up cytokine/creatinine ratios were significant for IL-1 beta, IL-6, and IL-8 (P < 0.01). Differences between pre-antibiotic and control cytokine/creatinine ratios were also significant for IL-1 beta, IL-6, and IL-8 (P < 0.01). Our study revealed that the urinary tract cytokine response to infection is intense but dissipates shortly after the initiation of antibiotic treatment. This suggests that renal damage due to inflammation begins early in infection, underscoring the need for rapid diagnosis and intervention.

Anti-Bacterial Agents↗
PubMed2001

Commonly used antibacterial and antifungal agents for hospitalised paediatric patients: implications for therapy with an emphasis on clinical pharmacokinetics.

Due to normal growth and development, hospitalised paediatric patients with infection require unique consideration of immune function and drug disposition. Specifically, antibacterial and antifungal pharmacokinetics are influenced by volume of distribution, drug binding and elimination, which are a reflection of changing extracellular fluid volume, quantity and quality of plasma proteins, and renal and hepatic function. However, there is a paucity of data in paediatric patients addressing these issues and many empiric treatment practices are based on adult data. The penicillins and cephalosporins continue to be a mainstay of therapy because of their broad spectrum of activity, clinical efficacy and favourable tolerability profile. These antibacterials rapidly reach peak serum concentrations and readily diffuse into body tissues. Good penetration into the cerebrospinal fluid (CSF) has made the third-generation cephalosporins the agents of choice for the treatment of bacterial meningitis. These drugs are excreted primarily by the kidney. The carbapenems are broad-spectrum beta-lactam antibacterials which can potentially replace combination regimens. Vancomycin is a glycopeptide antibacterial with gram-positive activity useful for the treatment of resistant infections, or for those patients allergic to penicillins and cephalosporins. Volume of distribution is affected by age, gender, and bodyweight. It diffuses well across serous membranes and inflamed meninges. Vancomycin is excreted by the kidneys and is not removed by dialysis. The aminoglycosides continue to serve a useful role in the treatment of gram-negative, enterococcal and mycobacterial infections. Their volume of distribution approximates extracellular space. These drugs are also excreted renally and are removed by haemodialysis. Passage across the blood-brain barrier is poor, even in the face of meningeal inflammation. Low pH found in abscess conditions impairs function. Toxicity needs to be considered. Macrolide antibacterials are frequently used in the treatment of respiratory infections. Parenteral erythromycin can cause phlebitis, which limits its use. Parenteral azithromycin is better tolerated but paediatric pharmacokinetic data are lacking. Clindamycin is frequently used when anaerobic infections are suspected. Good oral absorption makes it a good choice for step-down therapy in intra-abdominal and skeletal infections. The use of quinolones in paediatrics has been restricted and most information available is in cystic fibrosis patients. High oral bioavailability is also important for step-down therapy. Amphotericin B has been the cornerstone of antifungal treatment in hospitalised patients. Its metabolism is poorly understood. The half-life increases with time and can be as long as 15 days after prolonged therapy. Oral absorption is poor. The azole antifungals are being used increasingly. Fluconazole is well tolerated, with high bioavailability and good penetration into the CSF. Itraconazole has greater activity against aspergillus, blastomycosis, histoplasmosis and sporotrichosis, although it's pharmacological and toxicity profiles are not as favourable.

Anti-Bacterial Agents↗
PubMed2000

New insights on the origins of the stereocontrol of the staudinger reaction: [2 + 2] cycloaddition between ketenes and N-silylimines.

Density-functional theory studies on the [2 + 2] reaction between N-silylimines and ketenes to form the corresponding 2-azetidinones (beta-lactams) help to clarify several aspects on the mechanism of the Staudinger reaction. This reaction has been studied experimentally by Panunzio et al. It is shown that the formation of the 2-azetidinone ring takes place via two consecutive reactions. The first reaction consists of the nucleophilic addition of the iminic nitrogen to the sp-hybridized carbon atom of the ketene, with simultaneous migration of the silyl group from the imine to the oxygen atom of the ketene. This leads to silyl enol intermediates, in good agreement with the experimental results. Formation of the N-silylated beta-lactam takes place via a domino reaction consisting of a conrotatory thermal electrocyclization followed by a new silatropic rearrangement. It is also found that isomerization of the starting N-silylimine has a lower activation barrier than that associated with the formation of the C-N bond, which explains the stereochemical outcome experimentally observed. Further considerations on the asymmetric torquoelectronic effects involved in this reaction are also reported.

Journal Article↗
PubMed2000

A randomized, double-blind comparative trial evaluating the safety of liposomal amphotericin B versus amphotericin B lipid complex in the empirical treatment of febrile neutropenia. L Amph/ABLC Collaborative Study Group.

In this double-blind study to compare safety of 2 lipid formulations of amphotericin B, neutropenic patients with unresolved fever after 3 days of antibacterial therapy were randomized (1:1:1) to receive amphotericin B lipid complex (ABLC) at a dose of 5 mg/kg/d (n=78), liposomal amphotericin B (L Amph) at a dose of 3 mg/kg/d (n=85), or L Amph at a dose of 5 mg/kg/d (n=81). L Amph (3 mg/kg/d and 5 mg/kg/d) had lower rates of fever (23.5% and 19.8% vs. 57.7% on day 1; P<.001), chills/rigors (18.8% and 23.5% vs. 79.5% on day 1; P<.001), nephrotoxicity (14.1% and 14.8% vs. 42.3%; P<.01), and toxicity-related discontinuations of therapy (12.9% and 12.3% vs. 32.1%; P=.004). After day 1, infusional reactions were less frequent with ABLC, but chills/rigors were still higher (21.0% and 24.3% vs. 50.7%; P<.001). Therapeutic success was similar in all 3 groups.

Adolescent↗
PubMed2000

New stereoselective intramolecular

Efficient 1,4-asymmetric induction has been achieved in the highly stereocontrolled intramolecular [2 + 2] cycloadditions between ketenimines and imines, leading to 1,2-dihydroazeto[2, 1-b]quinazolines. The chiral methine carbon adjacent to the iminic nitrogen controls the exclusive formation of the cycloadducts with relative trans configuration at C2 and C8. The stepwise mechanistic model, based on theoretical calculations, fully supports the stereochemical outcome of these cycloadditions.

Journal Article↗
PubMed2000

Berberine cation: A fluorescent chemosensor for alkanes and other low-polarity compounds. An explanation of this phenomenon

Alkanes in the presence of berberine sulfate provide an enhancement of fluorescent signal, which depends on alkane concentration and structure, when the system is irradiated with monochromatic UV light. Computational analysis suggests that an ion-induced dipole between alkanes and berberine sulfate is responsible for this phenomenon. This interaction can properly model the experimentally obtained fluorescent response. The proposed explanation allows other interacting systems to be designed, which have been experimentally confirmed.

Journal Article↗
PubMed2000

Highly efficient induction of chirality in intramolecular

Highly stereocontrolled, intramolecular [2 + 2] cycloadditions between ketenimines and imines leading to 1,2-dihydroazeto[2, 1-b]quinazolines have been achieved. The source of stereocontrol is a chiral carbon atom adjacent either to the iminic carbon or nitrogen atom. In the first case, the stereocontrol stems from the preference for the axial conformer in the first transition structure. In the second case, the origin of the stereocontrol lies on the two-electron stabilizing interaction between the C-C bond being formed and the sigma orbital corresponding to the polar C-X bond, X being an electronegative atom. These models can be extended to other related systems for predicting the stereochemical outcome in this intramolecular reaction.

Journal Article↗
PubMed2000

Enhancement of fluorescence in thin-layer chromatography induced by the interaction between n-alkanes and an organic cation

Fluorescence enhancement of a broad variety of solutes has been used extensively in TLC although no thorough explanation has been proposed. In this work, we try to understand it and explore new applications to which it can be put. In this way, alkanes can be quantitatively determined by fluorescence scanning densitometry using silica gel plates impregnated with berberine sulfate. Molecular simulation and analysis of molecular orbitals allows this phenomenon to be explained in this case and lays the groundwork to explain fluorescence enhancements produced by other molecules. A ion-molecule interaction between alkanes and berberine sulfate is responsible for the enhancement of fluorescence produced by alkanes. Computational results suggest that the surrounding alkane molecules provide an apolar environment to the berberine cation, thus enhancing the intensity of the fluorescence signal. This proposed explanation has been tested by extending the fluorescence determination to other compounds. These include biologically interesting saturated and unsaturated fatty acids, steroids and derivatives, prostaglandins, ceramides, galactocerebrosides, as well as terpenes, and polypropylene glycols. In addition, according to the proposed explanation, the properties required for alternative impregnants to berberine are discussed.

Journal Article↗
PubMed1999

Antibodies to gliadin, endomysium, and tissue transglutaminase for the diagnosis of celiac disease.

BACKGROUND: Tissue transglutaminase has recently been identified as the main autoantigen recognized by antiendomysial antibodies in celiac disease. Serum immunoglobulin (Ig)A antibodies to tissue transglutaminase (tTG-ab) determined by an enzyme-linked immunosorbent assay (ELISA) technique have been reported to correlate closely with IgA antiendomysial antibodies (EMA). The purpose of this study was to assess the sensitivity, specificity, and predictive value of tTG-ab measured by a commercially available ELISA technique, compared with those of EMA and IgA antigliadin antibodies (AGA) for the diagnosis of celiac disease. METHODS: Twenty-seven serum samples were obtained from patients with untreated celiac disease, 37 from patients who had had gluten withdrawn from their diets for varying time spans, and 34 from control subjects without celiac disease. All were younger than 14 years. Presence of tTG-ab and AGA was determined by ELISA and of EMA by indirect immunofluorescence. RESULTS: Twenty-six of 27 serum samples obtained from patients at the time of diagnosis of celiac disease were AGA positive. All 27 (concordance rate 100%) were positive for EMA and tTG-ab. Of the 34 control subjects, 1 was for AGA and 2 for tTG-ab. All 34 were negative for EMA. Sensitivity, specificity, positive predictive value, and negative predictive value within this group were, for tTG-ab: 100%, 94%, 93%, and 100%, respectively; for EMA: all four indexes were 100%; and for AGA: 96%, 97%, 96%, and 97%, respectively. Of the 37 with treated celiac disease, 2 were AGA positive, 9 were EMA positive, and 6 were tTG-ab positive. The concordance rate between EMA and tTG-ab was 100% in the group with untreated celiac disease, 94% in the control subjects, and 76% in the group with treated celiac disease. CONCLUSIONS: Immunoglobulin A antibodies to tissue transglutaminase are new, highly sensitive, and specific markers of celiac disease. They can be determined easily by an accurate, comparatively cheap technique and thereby may advantageously replace the EMA marker traditionally used.

Adolescent↗
PubMed1998

Association of insulin-dependent diabetes mellitus and celiac disease: a study based on serologic markers.

BACKGROUND: The association of celiac disease and insulin-dependent diabetes mellitus has been known for some time. In an attempt to clarify this association, the prevalence of celiac disease among diabetic children was determined, and the risk of insulin-dependent diabetes mellitus was defined in pediatric patients with celiac disease. METHODS: Ninety-three children with diabetes were analyzed for the presence of celiac disease-related markers (antigliadin and antiendomysial antibodies) and characteristic alterations in the intestinal mucosa. In another group, 93 children with celiac disease were screened for pancreatic autoantibodies and pancreatic beta-cell function. RESULTS: Among children with insulin-dependent diabetes mellitus, a 6.45% prevalence of celiac disease was observed, a value significantly higher than that found among healthy controls. In contrast, only three celiac disease patients showed potential autoimmunity toward the pancreatic beta cell, a proportion not significantly different from that in the general population. Additionally, no alteration of glucose metabolism was observed in the antibody-positive patients. CONCLUSION: The increased risk of celiac disease among patients with diabetes requires a long follow-up to determine the presence of celiac disease markers among patients with diabetes, to avoid potential malignant disease derived from untreated celiac disease. In contrast, there is no evidence to support an increased risk of insulin-dependent diabetes mellitus among children with celiac disease. In accordance with the accepted influence of diet in the development of autoimmune diabetes, a hypothetical mechanism of protection against insulin-dependent diabetes mellitus that is mediated by environmental factors related to restricted diet is suggested in this population.

Adolescent↗