Biomedical subjects

César Sánchez

Publications and source records attributed to César Sánchez.

18 recordsLinked to original sources

PubMed2007

Early transpyloric enteral nutrition in critically ill children.

OBJECTIVE: We compared the tolerance of early (within the first 24 h after admission to the pediatric intensive care unit) and late transpyloric enteral nutrition in critically ill children. METHODS: We performed a prospective observational study including all critically ill children fed using transpyloric enteral nutrition. The clinical characteristics, energy intake, tolerance, and complications of nutritional delivery between the children with early (first 24 h) and late (after 24 h, range 1-43 d) transpyloric enteral nutrition were compared. RESULTS: Transpyloric nutrition was started within the first 24 h in 202 (38.5%) of the 526 children. There were no differences in the diagnoses, incidence of organ disturbances, doses of vasoactive drugs, or mortality between the two groups. There were no differences in the maximum number of calories delivered or in the duration of the nutrition between children with early and late transpyloric nutrition. The incidence of abdominal distention was lower in the children receiving early transpyloric nutrition (3.5%) than in those receiving nutrition at a later date (7.8%; P < 0.05). Moreover, 6.3% of patients presented diarrhea, with no difference being found between the two groups. CONCLUSION: Early transpyloric enteral nutrition is well tolerated in critically ill children and is not associated with an increase in incidence of complications.

Adolescent↗

PubMed2006

Indolocarbazole natural products: occurrence, biosynthesis, and biological activity.

The indolocarbazole family of natural products, including the biosynthetically related bisindolylmaleimides, is reviewed (with 316 references cited). The isolation of indolocarbazoles from natural sources and the biosynthesis of this class of compounds are thoroughly reviewed, including recent developments in molecular genetics, enzymology and metabolic engineering. The biological activities and underlying modes of action displayed by natural and synthetic indolocarbazoles is also presented, with an emphasis on the development of analogs that have entered clinical trials for its future use against cancer or other diseases.

Biological Products↗

PubMed2006

Transpyloric enteral nutrition in the critically ill child with renal failure.

OBJECTIVE: To study the efficacy and tolerance of transpyloric enteral nutrition (TEN) in the critically ill child with acute renal failure (ARF). DESIGN: Prospective observational study. SETTING: Paediatric intensive care unit. PATIENTS: Critically ill children with ARF who received TEN were included in the study. They were compared with the remaining 473 critically ill children receiving TEN in this period. Tolerance of nutrition and gastrointestinal complications were assessed. INTERVENTION: Transpyloric enteral nutrition. MEASUREMENTS AND RESULTS: Fifty-three critically ill children with ARF aged between 3 days and 17 years received TEN. Children with ARF more frequently received parenteral nutrition before TEN (56.6%) than the other patients (17.5%). The incidence of shock, hepatic alterations and mortality was significantly higher in patients with ARF than in the remaining children. In children with ARF the mean duration of the TEN was 16.5-27.3 days and the maximum caloric intake was 77-26.7 kcal/kg/day. Thirteen patients (24.5%) presented gastrointestinal complications, 9 (17%) abdominal distension and/or excessive gastric residue, 5 (9.4%) diarrhoea, 1 necrotising enterocolitis and 1 duodenal perforation. The frequency of gastrointestinal complications was significantly higher in children with ARF. TEN was definitive suspended in five patients due to gastrointestinal complications. Four of these patients were treated with continuous renal replacement therapy. Thirty percent of patients died during TEN. In only one patient was the death related to complications of the nutrition. CONCLUSIONS: Critically ill children with ARF tolerate TEN, although the incidence of gastrointestinal complications is higher than in other critically ill children.

Acute Kidney Injury↗

PubMed2006

Correlation between cardiac output measured by the femoral arterial thermodilution technique pulmonary arterial and that measured by contour pulse analysis in a paediatric animal model.

OBJECTIVE: To evaluate the correlation between two methods for the determination of cardiac output: the femoral arterial thermodilution technique (FATD) and the arterial pulse contour analysis (PCCO) using the PiCCO catheter. METHODS: We performed a prospective animal study using 51 immature Maryland pigs weighing 9 to 16 kg. A 4- or 5-Fr arterial PiCCO catheter was introduced into the femoral artery. In each animal, we made measurements of cardiac output at 30-minute intervals by femoral arterial thermodilution for a total of 209 measurements. We registered the previous PCCO and compared with the mean of two measures of FATD cardiac output. RESULTS: Mean FATD was 1.73 +/- 0.60 L/min and mean PCCO was 1.78 +/- 0.70 L/min (no significant difference). The mean difference (bias) of differences (limits of agreement) was 0.04. The correlation founded between the two methods was 0.786 (95% confidence interval, 0.71-0.83). CONCLUSIONS: Femoral arterial thermodilution cardiac output measurements correlates well with pulse contour analysis cardiac output in this paediatric animal model.

Aging↗

PubMed2006

Engineering biosynthetic pathways to generate antitumor indolocarbazole derivatives.

The indolocarbazole family of natural products is a source of lead compounds with potential therapeutic applications in the treatment of cancer and neurodegenerative disorders. Rebeccamycin and staurosporine are two members of this family, which are produced by different actinomycete strains. Although both compounds display antitumor activity, their distinct structural features determine different modes of action: rebeccamycin targets DNA topoisomerase I, while staurosporine is a protein kinase inhibitor. Here we examine the biosyntheses of rebeccamycin and staurosporine while we summarize our recent work concerning (a) identification and characterization of genes involved in the biosynthesis of indolocarbazoles in actinomycetes, and (b) generation of novel indolocarbazole derivatives in microorganisms by combinatorial biosynthesis.

Antibiotics, Antineoplastic↗

PubMed2006

Haemodynamic response to acute hypovolaemia, rapid blood volume expansion and adrenaline administration in an infant animal model.

We performed a prospective experimental animal study in seven sedated and mechanically ventilated piglets weighing 9+/-0.8 kg, to assess the haemodynamic response to acute hypovolaemia, rapid blood volume expansion and adrenaline (epinephrine) administration in an infant animal model. Withdrawal of 20 mL/kg of blood (hypovolaemia), rapid infusion of 20 mL/kg of blood (expansion) and the administration of 0.01 mg/kg of adrenaline were made in each animal. Heart rate, mean blood pressure (MBP), central venous pressure (CVP), pulmonary capillary pressure (PCP), cardiac index (CI), systemic vascular resistance index (SVRI), left ventricular contractility (Dp/dtmax), blood volume variables, including intrathoracic blood volume index (ITBI), global end-diastolic volume (GEDVI) and extravascular lung water index (ELWI). Hypovolaemia produced a significant decrease in the pressure, volume and CI variables, with an increase in SVRI and a decrease in Dp/dtmax. After expansion, all variables returned towards normal, with persistence of the SVRI increase and Dp/dtmax decrease. Changes in the blood volume variables (ITBI and GEDVI) were larger than in the pressure variables (CVP, PCP) in the case of both hypovolaemia and expansion. Adrenaline caused a slight increase in heart rate, MBP, CVP, PCP and Dp/dtmax with a greater increase in SVRI. None of the interventions led to changes in ELWI. We conclude that acute hypovolaemia produces an increase in SVRI and a decrease in Dp/dtmax that does not return fully to normal with restoration of blood volume. ITBI and GEDVI are more sensitive to changes in blood volume than CVP and PCP. Rapid blood volume expansion and adrenaline administration do not affect extravascular lung water.

Acute Disease↗

PubMed2006

Reevaluation of the violacein biosynthetic pathway and its relationship to indolocarbazole biosynthesis.

The biosynthetic pathways for violacein and for indolocarbazoles (rebeccamycin, staurosporine) include a decarboxylative fusion of two tryptophan units. However, in the case of violacein, one of the tryptophans experiences an unusual 1-->2 shift of the indole ring. The violacein biosynthetic gene cluster was previously reported to consist of four genes, vioABCD. Here we studied the violacein pathway through expression of vio genes in Escherichia coli and Streptomyces albus. A pair of genes (vioAB), responsible for the earliest steps in violacein biosynthesis, was functionally equivalent to the homologous pair in the indolocarbazole pathway (rebOD), directing the formation of chromopyrrolic acid. However, chromopyrrolic acid appeared to be a shunt product, not a violacein intermediate. In addition to vioABCD, a fifth gene (vioE) was essential for violacein biosynthesis, specifically for production of the characteristic 1-->2 shift of the indole ring. We also report new findings on the roles played by the VioC and VioD oxygenases, and on the origin of violacein derivatives of the chromoviridans type.

Bacterial Proteins↗

PubMed2006

Transpyloric enteral feeding in the postoperative of cardiac surgery in children.

PURPOSE: The aim of this study is to assess the utility of transpyloric enteral nutrition in the postoperative period of cardiac surgery in children. METHODS: A prospective, observational study was performed on children receiving transpyloric enteral nutrition in the postoperative period of cardiac surgery. The type of nutrition, duration, tolerance, and complications were studied. RESULTS: Children (212) between the ages of 3 days and 17 years received transpyloric enteral nutrition in the postoperative period of cardiac surgery. The duration of the transpyloric feeding was 16 +/- 23.8 days, and the maximum calorie delivery was 85.1 +/- 25.7 kcal/kg/d. Tolerance to nutrition was good and was not affected by the infusion of vasoactive drugs, sedatives, or muscle relaxants. Of the study population, 14.6% presented with gastrointestinal complications, 9.4% with abdominal distension and/or excessive gastric residue, and 7.5% with diarrhea. Nutrition was withdrawn in 2.4% of the patients because of gastrointestinal complications. Mortality was not related to any characteristic of the nutrition or to gastrointestinal complications. CONCLUSIONS: Transpyloric enteral nutrition is useful and is a simple feeding method that enables a high calorie delivery to be provided with few complications in the postoperative period of cardiac surgery in children, including those receiving high doses of sedatives and muscle relaxants.

Adolescent↗

PubMed2006

Effects of initiation of continuous renal replacement therapy on hemodynamics in a pediatric animal model.

There are no studies analyzing the initial hemodynamic impact of continuous renal replacement therapy (CRRT) in children. We have performed a prospective observational study in 34 immature Maryland pigs to analyze the initial hemodynamic changes during venovenous CRRT. The heart rate, blood pressure, central venous pressure (CVP), pulmonary arterial occlusion pressure (PAOP), pulmonary capillary wedge pressure, temperature, and cardiac output (CO), simultaneously by pulmonary arterial thermodilution and femoral arterial thermodilution, were measured at 30-min intervals during 2 h. Venovenous CRRT induced an initial significant diminution of volemic hemodynamic parameters (intrathoracic blood volume, global end-diastolic volume, stroke volume index, PAOP, and CVP). Simultaneously, a significant increase in systemic vascular resistance index and left ventricular contractility, and a decrease in CO, was observed. We conclude that CRRT in a pediatric animal model induces initial hypovolemia, and a systemic cardiovascular response with vasoconstriction and increase in ventricular contractility.

Age Factors↗

PubMed2006

Estimation of the parameters of cardiac function and of blood volume by arterial thermodilution in an infant animal model.

BACKGROUND: Experimental studies in adults and in animals have reported that estimation of the intracardiac volumes by arterial thermodilution is a more reliable method of blood volume estimation than pressure measurement. The objective of this study has been to analyze the values of cardiac function and blood volume in an infant animal model using the arterial thermodilution technique. METHODS: A total of 202 measurements of cardiac output were performed by femoral arterial thermodilution in 38 Maryland piglets weighing between 8 and 16 kg, to determine the normal values of blood volume obtained by arterial thermodilution (PiCCO method) in an infant animal model. The following parameters were measured: blood volume [global end-diastolic volume index (GEDVI), total intrathoracic blood index (ITBI), extravascular lung water index (ELWI), systolic volume index (SVI)] and parameters of cardiac and vascular function [systolic volume index (SVI), cardiac function index (CFI), left ventricular contractility (Dp/dtmax), and systemic vascular resistance index) (SVRI)]. RESULTS: The cardiac index, 4.3 +/- 1.2 l x min(-1) x m(2), was within the normal range. The GEDVI, 198 +/- 48.6 ml x m(2), and ITBI, 574.1 +/- 113.4 ml x m(2), were lower than the normal values reported in adults, whereas the ELWI, 16.3 +/- 5.2 ml x kg(-1), was higher. CONCLUSIONS: Intrathoracic and intracardiac volume values obtained by arterial thermodilution are lower than those considered normal in the adult, whereas the extravascular lung water is higher. These values must be taken into account when the PiCCO method is used in small children.

Animals↗

PubMed2006

Continuous venovenous renal replacement therapy with a pulsatile tubular blood pump: analysis of efficacy parameters.

A three-valve pulsatile tubular pump was used in 10 pigs weighing 9.9+/-0.3 kg, connected to a neonatal hemofiltration (HF) circuit to analyze the parameters to determine the ultrafiltration effectiveness for venovenous continuous renal replacement therapy. Forty 30-min periods were studied to analyze the influence of the catheter diameter, purification technique (HF or hemodiafiltration), pump pulsation frequency, percentage time in diastole, percentage time in diastole in which the post pump valve was closed, and percentage time in systole in which the post filter valve was closed, on ultrafiltrate volume and blood flow through the filter. A higher ultrafiltrate flow was achieved with a frequency of 60 bpm than with 30 bpm, a diastolic time of 65% of the total cycle versus 50%, and a blood flow of greater than 20 mL/min versus less than 20 mL/min. The ultrafiltrate flow increases in relation to the blood flow, the frequency of the pump, and the diastolic time.

Animals↗

PubMed2005

Deciphering the late steps in the biosynthesis of the anti-tumour indolocarbazole staurosporine: sugar donor substrate flexibility of the StaG glycosyltransferase.

The indolocarbazole staurosporine is a potent inhibitor of a variety of protein kinases. It contains a sugar moiety attached through C-N linkages to both indole nitrogen atoms of the indolocarbazole core. Staurosporine biosynthesis was reconstituted in vivo in a heterologous host Streptomyces albus by using two different plasmids: the 'aglycone vector' expressing a set of genes involved in indolocarbazole biosynthesis together with staG (encoding a glycosyltransferase) and/or staN (coding for a P450 oxygenase), and the 'sugar vector' expressing a set of genes responsible for the biosynthesis of the sugar moiety. Attachment of the sugar to the two indole nitrogens of the indolocarbazole core was dependent on the combined action of StaG and StaN. When StaN was absent, the sugar was attached only to one of the nitrogen atoms, through an N-glycosidic linkage, as in the indolocarbazole rebeccamycin. The StaG glycosyltransferase showed flexibility with respect to the sugar donor. When the 'sugar vector' was substituted by constructs directing the biosynthesis of l-rhamnose, L-digitoxose, L-olivose and D-olivose, respectively, StaG and StaN were able to transfer and attach all of these sugars to the indolocarbazole aglycone.

Bacterial Proteins↗

PubMed2004

Combinatorial biosynthesis of antitumor indolocarbazole compounds.

Rebeccamycin and staurosporine are natural products with antitumor properties, which belong to the family of indolocarbazole alkaloids. An intense effort currently exists for the generation of indolocarbazole derivatives for the treatment of several diseases, including cancer and neurodegenerative disorders. Here, we report a biological process based on combinatorial biosynthesis for the production of indolocarbazole compounds (or their precursors) in engineered microorganisms as a complementary approach to chemical synthesis. We have dissected and reconstituted the entire biosynthetic pathway for rebeccamycin in a convenient actinomycete host, Streptomyces albus. This task was achieved by coexpressing different combinations of genes isolated from the rebeccamycin-producing microorganism. Also, a gene (staC) was identified in staurosporine-producing microbes and was shown to have a key role to differentiate the biosynthetic pathways for the two indolocarbazoles. Last, incorporation of the pyrH and thal genes, encoding halogenases from different microorganisms, resulted in production of derivatives with chlorine atoms at novel positions. We produced >30 different compounds by using the recombinant strains generated in this work.

Antineoplastic Agents↗

PubMed2004

Biosynthesis of the angiogenesis inhibitor borrelidin by Streptomyces parvulus Tü4055: cluster analysis and assignment of functions.

The biosynthetic gene cluster for the angiogenesis inhibitor borrelidin has been cloned from Streptomyces parvulus Tü4055. Sequence analysis indicates that the macrolide ring of borrelidin is formed by a modular polyketide synthase (PKS) (borA1-A6), a result that was confirmed by disruption of borA3. The borrelidin PKS is striking because only seven rather than the nine modules expected for a nonaketide product are encoded by borA1-A6. The starter unit of the PKS has been verified as trans-cyclopentane-1,2-dicarboxylic acid (trans-1,2-CPDA), and the genes involved in its biosynthesis identified. Other genes responsible for biosynthesis of the nitrile moiety, regulation, and self-resistance were also identified.

Angiogenesis Inhibitors↗

PubMed2004

Atrial activity extraction for atrial fibrillation analysis using blind source separation.

This contribution addresses the extraction of atrial activity (AA) from real electrocardiogram (ECG) recordings of atrial fibrillation (AF). We show the appropriateness of independent component analysis (ICA) to tackle this biomedical challenge when regarded as a blind source separation (BSS) problem. ICA is a statistical tool able to reconstruct the unobservable independent sources of bioelectric activity which generate, through instantaneous linear mixing, a measurable set of signals. The three key hypothesis that make ICA applicable in the present scenario are discussed and validated: 1) AA and ventricular activity (VA) are generated by sources of independent bioelectric activity; 2) AA and VA present non-Gaussian distributions; and 3) the generation of the surface ECG potentials from the cardioelectric sources can be regarded as a narrow-band linear propagation process. To empirically endorse these claims, an ICA algorithm is applied to recordings from seven patients with persistent AF. We demonstrate that the AA source can be identified using a kurtosis-based reordering of the separated signals followed by spectral analysis of the sub-Gaussian sources. In contrast to traditional methods, the proposed BSS-based approach is able to obtain a unified AA signal by exploiting the atrial information present in every ECG lead, which results in an increased robustness with respect to electrode selection and placement.

Algorithms↗

PubMed2002

Continuous venovenous renal replacement therapy using a pulsatile blood pump.

The objective of this study was to evaluate the efficacy of a pulsatile pump for continuous renal replacement therapy in a pediatric-size animal model. A vacuum-driven, tubular, blood-pumping device was used in 13 pigs weighing 10.4+/-1.5 kg, connected to a neonatal hemofiltration circuit with an FH22 filter and a flow sensor. Three different flow rates [30 ml/min (8 cases), 15 ml/min (3 cases), and 5 ml/min (2 cases] were used over 2-h periods. Aspiration pressure, frequency of pulsation, blood flow rate, ultrafiltrate volume, pre- and post-filter pressures, heart rate, arterial blood pressure, temperature, pH, sodium, potassium, chloride, urea, creatinine, glucose, and hematocrit were measured at 30-min intervals. The mean ultrafiltrate flow was 0.54+/-0.33 ml/kg per min. The aspiration pressure and pulsation frequency needed to maintain blood flow remained stable throughout the experiment. There were no complications secondary to the use of this technique and no significant changes in heart rate, blood pressure, or analytical determinations. In conclusion, in this animal model, the pulsatile pump has been shown to be an effective method for continuous venovenous renal replacement therapy.

Animals↗

PubMed2002

The biosynthetic gene cluster for the antitumor rebeccamycin: characterization and generation of indolocarbazole derivatives.

Rebeccamycin, a halogenated natural product of the indolocarbazole family, is produced by Saccharothrix aerocolonigenes ATCC39243. Several rebeccamycin analogues, which target DNA topoisomerase I or II, have already entered clinical trials as anticancer drugs. Using as a probe an internal fragment of ngt, a Saccharothrix aerocolonigenes gene encoding an indolocarbazole N-glycosyltransferase, we isolated a DNA region that directed the biosynthesis of rebeccamycin when introduced into Streptomyces albus. Sequence analysis of 25.6 kb revealed genes for indolocarbazole core formation, halogenation, glycosylation, and sugar methylation, as well as a regulatory gene and two resistance/secretion genes. Heterologous expression of subsets of these genes resulted in production of deschloro-rebeccamycin, 4'-demethyldeschloro-rebeccamycin, and deschloro-rebeccamycin aglycone. The cloned genes should help to elucidate the molecular basis for indolocarbazole biosynthesis and set the stage for the generation of novel indolocarbazole analogues by genetic engineering.

Actinomycetales↗

PubMedDate not supplied

Comparison of a tubular pulsatile pump and a volumetric pump for continuous venovenous renal replacement therapy in a pediatric animal model.

We compare the efficacy of a tubular pulsatile pump and a conventional volumetric pump (IVAC 571), connected to a neonatal hemofiltration circuit with an FH22 filter, for continuous renal replacement therapy in 54 Maryland pigs weighing 8-16 kg. Three different flow rates (30 ml/min in 12 cases, 15 ml/min in 22 cases, and 5 ml/min in 20 cases) were used over a 2-hour period. Hemofiltration and hemodiafiltration were performed, and measurements of ultrafiltrate flow, circuit pressures, heart rate, blood pressure, temperature, urea, creatinine, total proteins, Na, K, Cl, hematocrit, and hemolysis parameters (aspartate transaminase, lactic dehydrogenase, haptoglobin, indirect bilirubin, free hemoglobin) were made. There were no differences in ultrafiltrate flow between the two pumps. Ultrafiltrate volume was significantly higher with higher flows (p < 0.01). The technique was well tolerated by all pigs. When each blood flow was analyzed separately, cross-filter pressure drop was significantly higher in the volumetric pump than in the tubular pulsatile pump (p < 0.05). No significant differences in heart rate, blood pressure, or analytical determinations were seen between the two pumps. We conclude that pulsatile and volumetric pumps can be uses as an alternative to roller pumps for continuous venovenous renal replacement therapy in neonates and infants.

Animals↗