Enteral nutrition volume is not correlated with lower respiratory tract infection in patients on mechanical ventilation / El volumen de nutrición enteral no se correlaciona con las infecciones del tracto respiratorio inferior en pacientes con ventilación mecánica

Objective: To evaluate the effect of enteral nutrition volume, gastrointestinal function and the type of acid suppressive drug upon the incidence of lower respiratory tract infections in critically ill patients on mechanical ventilation (MV). Design: A retrospective secondary analysis was carried out. Setting: The Intensive Care Unit of a University Hospital. Patients or participants: Patients≥18-years-old expected to need MV for more than four days, and receiving enteral nutrition by nasogastric tube within 24h of starting MV. Interventions: We correlated enteral nutrition volume administered during the first 10 days, gastrointestinal function and the type of acid suppressive therapy with the episodes of lower respiratory tract infection up until day 28. Cox proportional hazards ratios in univariate and adjusted multivariate models were used. Statistical significance was considered for p<0.05. Main variables of interest: Lower respiratory tract infection episodes. Results: Sixty-six out of 185 patients (35.7%) had infection; 27 patients had ventilator-associated pneumonia; and 39 presented ventilator-associated tracheobronchitis. Uninfected and infected groups were similar in terms of enteral nutrition volume (54±12 and 54±9mL/h; p=0.94) and caloric intake (19.4±4.9 and 19.6±5.2kcal/kg/d; p=0.81). The Cox proportional hazards model showed neurological indication of MV to be the only independent variable related to infection (p=0.001). Enteral nutrition volume, the type of acid suppressive therapy, and the use of prokinetic agents were not significantly correlated to infection. Conclusions: Enteral nutrition volume and caloric intake, gastrointestinal dysfunction and the type of acid suppressive therapy used were not associated to lower respiratory tract infection in patients on MV (AU)

Objetivo: Valorar el efecto del volumen de nutrición enteral, la función gastrointestinal y el tipo de protección gástrica en la incidencia de infección respiratoria del tracto inferior en pacientes críticos con ventilación mecánica (VM). Diseño: Análisis secundario retrospectivo. Ámbito: La Unidad de Cuidados Intensivos de un hospital universitario. Pacientes o participantes: Pacientes con edad≥18 años que se espera que precisen de VM durante>4 días y reciban nutrición enteral en las primeras 24h. Intervenciones: Correlacionamos el volumen de nutrición enteral administrado durante los primeros 10 días, la función gastrointestinal y el tipo de protección gástrica con los episodios de infección pulmonar del tracto inferior hasta el día 28. Utilizamos el modelo de regresión de Cox. Un valor de p<0,05 fue considerado estadísticamente significativo. Principal variable de interés: Episodios de infección del tracto respiratorio inferior. Resultados: Sesenta y seis de los 185 pacientes (35,7%) presentaron infección, 27 pacientes neumonía y 39 traqueobronquitis. Los pacientes no infectados e infectados fueron similares en el volumen de nutrición enteral (54±12 y 54±9mL/h; p=0,94) y aporte calórico (19,4±4,9 y 19,6±5,2kcal/kg/d; p=0,81). El modelo de regresión de Cox mostró que la causa neurológica de VM fue la única variable independiente asociada con infección (p=0,001). El volumen de nutrición enteral, el tipo de protección gástrica y la función gastrointestinal no se correlacionaron significativamente con la infección. Conclusiones: El volumen y aporte calórico de nutrición enteral, la disfunción gastrointestinal y el tipo de protección gástrica no se asociaron a la infección del tracto respiratorio inferior en pacientes con VM (AU)

Enteral nutrition volume is not correlated with lower respiratory tract infection in patients on mechanical ventilation.

OBJECTIVE: To evaluate the effect of enteral nutrition volume, gastrointestinal function and the type of acid suppressive drug upon the incidence of lower respiratory tract infections in critically ill patients on mechanical ventilation (MV). DESIGN: A retrospective secondary analysis was carried out. SETTING: The Intensive Care Unit of a University Hospital. PATIENTS OR PARTICIPANTS: Patients≥18-years-old expected to need MV for more than four days, and receiving enteral nutrition by nasogastric tube within 24h of starting MV. INTERVENTIONS: We correlated enteral nutrition volume administered during the first 10 days, gastrointestinal function and the type of acid suppressive therapy with the episodes of lower respiratory tract infection up until day 28. Cox proportional hazards ratios in univariate and adjusted multivariate models were used. Statistical significance was considered for p<0.05. MAIN VARIABLES OF INTEREST: Lower respiratory tract infection episodes. RESULTS: Sixty-six out of 185 patients (35.7%) had infection; 27 patients had ventilator-associated pneumonia; and 39 presented ventilator-associated tracheobronchitis. Uninfected and infected groups were similar in terms of enteral nutrition volume (54±12 and 54±9mL/h; p=0.94) and caloric intake (19.4±4.9 and 19.6±5.2kcal/kg/d; p=0.81). The Cox proportional hazards model showed neurological indication of MV to be the only independent variable related to infection (p=0.001). Enteral nutrition volume, the type of acid suppressive therapy, and the use of prokinetic agents were not significantly correlated to infection. CONCLUSIONS: Enteral nutrition volume and caloric intake, gastrointestinal dysfunction and the type of acid suppressive therapy used were not associated to lower respiratory tract infection in patients on MV.

El volumen de nutrición enteral no se correlaciona con las infecciones del tracto respiratorio inferior en pacientes con ventilación mecánica / The volume of enteral nutrition does not correlate with lower respiratory tract infections in patients with mechanical ventilation

Objetivo. Valorar el efecto del volumen de nutrición enteral, la función gastrointestinal y el tipo de protección gástrica en la incidencia de infección respiratoria del tracto inferior en pacientes críticos con ventilación mecánica (VM). Diseño Análisis secundario retrospectivo. Ámbito La Unidad de Cuidados Intensivos de un hospital universitario. Pacientes o participantes Pacientes con edad≥18 años que se espera que precisen de VM durante>4 días y reciban nutrición enteral en las primeras 24h. Intervenciones Correlacionamos el volumen de nutrición enteral administrado durante los primeros 10 días, la función gastrointestinal y el tipo de protección gástrica con los episodios de infección pulmonar del tracto inferior hasta el día 28. Utilizamos el modelo de regresión de Cox. Un valor de p<0,05 fue considerado estadísticamente significativo. Principal variable de interés Episodios de infección del tracto respiratorio inferior. Resultados Sesenta y seis de los 185 pacientes (35,7 por ciento) presentaron infección, 27 pacientes neumonía y 39 traqueobronquitis. Los pacientes no infectados e infectados fueron similares en el volumen de nutrición enteral (54±12 y 54±9mL/h; p=0,94) y aporte calórico (19,4±4,9 y 19,6±5,2kcal/kg/d; p=0,81). El modelo de regresión de Cox mostró que la causa neurológica de VM fue la única variable independiente asociada con infección (p=0,001). El volumen de nutrición enteral, el tipo de protección gástrica y la función gastrointestinal no se correlacionaron significativamente con la infección. Conclusiones El volumen y aporte calórico de nutrición enteral, la disfunción gastrointestinal y el tipo de protección gástrica no se asociaron a la infección del tracto respiratorio inferior en pacientes con VM.

[Signaling by melatonin receptors]. / Signalisation des récepteurs de la mélatonine.

Melatonin is a hormone involved in various physiological processes such as the circadian cycle, hormone release and immune response. High-affinity melatonin receptors are classified in two pharmacologically distinct groups: Mel1 and Mel2. These receptors have first been localized in different organs and brain structures and some subtypes have since been cloned. Inhibition of adenylyl cyclase by Mel1 receptors is the best investigated signalling pathway but cannot be entirely responsible for the diversity of melatonin-induced phenomena. Phospholipase C, potassium ion channels and guanylyl cyclases have also been reported to be modulated by melatonin. This review updates present knowledge of the characterization and signalization of melatonin receptors.

Novel isoforms of Mel1c melatonin receptors modulating intracellular cyclic guanosine 3',5'-monophosphate levels.

Two cDNAs encoding novel isoforms of Xenopus laevis melatonin receptors were cloned using PCR primers specific for the X. laevis-melanophore Mel1c melatonin receptor described in a recent publication. The novel isoforms were highly homologous to the described frog Mel1c cDNA, although the C-terminal tail of both was shorter by 65 amino acid residues. Nucleotide sequences of these novel isoforms, called Mel1c(alpha) and Mel1c(beta), differed from each other by only 35 nucleotides and six amino acid residues. Studies on several animals of various Xenopus species indicate that Mel1c(alpha) and Mel1c(beta) receptors may correspond to allelic variants of the same locus. Studies on cells transfected with both receptor cDNAs showed the expression of high-affinity 2-[125I]iodomelatonin binding sites. Agonist stimulation of Mel1c(alpha) receptor was associated with the inhibition of cAMP accumulation stimulated by forskolin (IC50 approximately 10(-10) M) in HeLa, Ltk-, and human embryonic kidney 293 (HEK 293) cells. Mel1c(beta) receptor modulated cAMP in HeLa and HEK 293 cells but not in Ltk- cells. Both receptors inhibited, in a dose-dependent manner, cGMP accumulation in all three cell lines incubated with a phosphodiesterase inhibitor. This effect was localized upstream of soluble guanylyl cyclase and was blocked by pertussis toxin treatment. However, IC50 values (approximately 10(-10) M for Mel1c(beta) and 10(-9) to 10(-7) M for Mel1c(alpha)) and maximal inhibition levels showed that Mel1c(alpha) receptors are much less efficiently coupled to the cGMP pathway. Coupling differences may be explained by the fact that five of the six amino acid substitutions between Mel1c(alpha) and Mel1c(beta) receptors are located within cytoplasmic regions potentially involved in signal transduction. The existence of coupling differences is in agreement with the observation that expression of both receptors is evolutionally conserved in native tissue. In conclusion, two novel, potentially allelic, isoforms of Xenopus Mel1c melatonin receptors display identical ligand-binding characteristics, but different potencies in modulating cAMP and cGMP levels through G(i)/G(o)-dependent pathways. Furthermore, to our knowledge, this study provides the first data on the modulation of intracellular cGMP levels by cloned melatonin receptors.

Synthesis and structure-activity relationships of novel naphthalenic and bioisosteric related amidic derivatives as melatonin receptor ligands.

A series of N-naphthylethyl amide derivatives were synthesized and evaluated as melatonin receptor ligands. The affinity of each compound for the melatonin receptor was determined by binding studies using [2-125I]iodomelatonin on ovine pars tuberalis membrane homogenates. Structure-activity relationships led to the conclusion that naphthalene is a bioisostere of the indole moiety of melatonin. Moreover it appears that the affinity is strongly affected by the size of the substituent of the nitrogen of the amidic function. Many of these ligands give biphasic dose-response curves which suggests that there may be two melatonin receptor subtypes within the ovine pars tuberalis cells. The replacement of naphthalene by benzofuran or benzothiophene did not strongly alter the affinity for the melatonin receptor. In contrast, the benzimidazole analogue was a poor ligand. Compound 7, the naphthalenic analogue of melatonin, a selective ligand of the melatonin receptor and an agonist derivative, has been selected for clinical development.

5-HT1A receptor agonists prevent in rats the yawning and penile erections induced by direct dopamine agonists.

The new compound (+) S-20499, an amino chromane derivative (8[-4[N-(5-methoxychromane-3yl)N-propyl]aminobutyl] azaspiro[4-5] décane-7,9 dione), is a high affinity full 5-HT1A agonist. We have investigated its effects on dopaminergic transmission. (+) S-20499 displayed a 10(-8) M affinity for D2 dopamine (DA) receptors, 100 fold lower than for 5-HT1A receptors. The hypothermic effect of the drug was reversed by haloperidol in mice, suggesting that it behaves as a direct dopamine agonist. However, increasing doses of (+) S-20499 induced neither yawning nor penile erections, which constitute characteristic responses of direct DA agonists administered at low doses. In addition, (+) S-20499 prevented the apomorphine (100 micrograms/kg SC) induced yawning and penile erections. This inhibition appears to result from the stimulation of 5-HT1A receptors since it is an effect shared by both buspirone (from 5 mg/kg) and 8-OH-DPAT (from 0.10 mg/kg). In addition, when rats are treated with the 5-HT1A receptor antagonist tertatolol (2-5 mg/kg; SC), increasing doses of (+) S-20499 elicit the expected yawns and penile erections. It is concluded that the 5-HT1A agonist property opposes to that of D2 dopamine receptor stimulation with regard to yawning and penile erections.

Protective effect of a purified flavonoid fraction against reactive oxygen radicals. In vivo and in vitro study.

S 5682 is a purified flavonoid fraction containing 90% diosmin (flavone derivative) and 10% hesperidin (flavanone derivative). In this study the scavenging properties of S 5682 on active oxygen radicals were demonstrated in vivo and in vitro. The activity of intravenous S 5682 was evaluated in the rat by measuring the degree of hyperglycemia provoked by an intravenous injection of alloxan, the metabolism of which produces active oxygen radicals which are toxic to B cells of the pancreas. S 5682 produced a decrease in the hyperglycemia in a dose-dependent manner (25 mg/kg and 50 mg/kg). The production in vitro of active oxygen radicals during phagocytosis by polymorphonuclear cells and macrophages is accompanied by emission of photons which can be amplified in the presence of luminol. Measurement of this chemiluminescence is a way of determining the quantity of active oxygen radicals generated in the medium, this may be reduced either by a decrease in production or by an increase in neutralisation through a reducing effect. Results demonstrated that S 5682 had a scavenging effect on active oxygen radicals for concentrations between 2 x 10(-8) mol/l and 2 x 10(-4) mol/l. The concentration of S 5682 reducing the chemiluminescence by 50% was 1.6 x 10(-5) mol/l. These scavenging properties imply that S 5682 has a pharmacological action on capillary hyperpermeability as well as an anti-inflammatory and anti-oedematous action.

l-fenfluramine and haloperidol in rats: a qEEG comparison.

EEG effects of l-fenfluramine (l-F) (2.5, 5 and 10 mg/kg) and haloperidol (0.1, 0.25 and 0.5 mg/kg) were studied in 20 adult rats. The EEG signals of two prefrontal (A = +4, L = 2.5) and two sensorimotor (A = -4, L = 4) transcortical electrodes were analyzed in each rat during three 60-min periods, 1, 3 and 5 h after the intraperitoneal (IP) administration of the drugs. In the prefrontal cortex haloperidol induced a decreased power for the 1-3 Hz components and an increase in power for frequencies higher than 8 Hz, with a maximum around 13 Hz. These effects were already observed after 0.1 mg/kg. In this cortical area l-F administration was essentially associated with a decrease of power maximum for 3-8 Hz, an increased power for the 10-19 Hz band being present only after 10 mg/kg. In the sensorimotor cortex haloperidol appeared less potent than in the prefrontal site; a significant power increase for the frequencies higher than 8 Hz was only observed with 0.5 mg/kg. On the contrary, l-F appeared more effective in this area, its action being characterized by a decreased power from 2-8 Hz and a power increase already significant with 2.5 mg/kg for the frequencies higher than 10 Hz, with a maximum lying around 15 Hz. These results suggest that haloperidol induced cortical sedation (increased power) on the two recording sites. l-F also induced a net cortical sedation in sensorimotor cortex but up to 5 mg/kg acted in the opposite direction on the prefrontal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)