Traqueobronquitis y neumonía asociada a ventilación mecánica por Chryseobacterium indologenes / Tracheo-bronchitis and pneumonia associated with mechanical ventilation by Chryseobacterium indologenes

El desarrollo de infecciones nosocomiales por gérmenes intrínsecamente resistentes a carbapenemes aumenta la mortalidad y provoca un aumento del gasto sanitario. El conocimiento y estudio de estas infecciones es importante a la hora de mejorar protocolos de actuación epidemiológicos y terapéuticos. Presentamos un estudio descriptivo, de 8 casos clínicos de pacientes con diagnóstico de traqueobronquitis y neumonía asociada a ventilación mecánica (NAVM) por Chryseobacterium indologenes (CBI), durante un periodo de 5 años. En esta serie de casos el aislamiento del CBI se produjo a los 11 días de media (rango 7-18) de permanecer los enfermos conectados a ventilación mecánica. La duración media de los pacientes en ventilación mecánica fue de 36 días (rango 10-140). La estancia media en UCI fue de 49 días (rango 14-180). Únicamente en un paciente no se aisló copatógeno concurrente a la traqueobronquitis o la NAVM por CBI. La mortalidad intrahospitalaria fue del 25%. La infección respiratoria nosocomial secundaria a CBI en pacientes con ventilación mecánica ha aumentado en los últimos años, por lo que se debería incluir en el diangóstico diferencial de la NAMV (AU)

The development of nosocomial infections by germs resistant to carbapenems inherently increases mortality, and causes an increase in health spending. The knowledge and study of these infections is important in improving epidemiological and therapeutic performance protocols. We present a descriptive study of eight patients diagnosed with tracheobronchitis (TAVM) and pneumonia (NAVM) associated with mechanical ventilation Chryseobacterium indologenes (CBI), over a period of five years. CBI isolation occurred at 11 days on average (rank 7-18) of remaining patients connected to mechanical ventilation. The average length of patients on mechanical ventilation was 36 days (range 10-140). The average ICU stay was 49 days (range 14-180). There was no death at 28 days, but the intra-hospital mortality was 2 cases (25%). Nosocomial respiratory infection secondary to CBI in mechanically ventilated patients has increased in recent years, so that should be included in the differential diagnostic of NAMV (AU)

Tracheo-bronchitis and pneumonia associated with mechanical ventilation by Chryseobacterium indologenes. / Traqueobronquitis y neumonía asociada a ventilación mecánica por Chryseobacterium indologenes.

The development of nosocomial infections by germs resistant to carbapenems inherently increases mortality, and causes an increase in health spending. The knowledge and study of these infections is important in improving epidemiological and therapeutic performance protocols. We present a descriptive study of eight patients diagnosed with tracheobronchitis (TAVM) and pneumonia (NAVM) associated with mechanical ventilation Chryseobacterium indologenes (CBI), over a period of five years. CBI isolation occurred at 11 days on average (rank 7-18) of remaining patients connected to mechanical ventilation. The average length of patients on mechanical ventilation was 36 days (range 10-140). The average ICU stay was 49 days (range 14-180). There was no death at 28 days, but the intra-hospital mortality was 2 cases (25%). Nosocomial respiratory infection secondary to CBI in mechanically ventilated patients has increased in recent years, so that should be included in the differential diagnostic of NAMV.

Vasorelaxant effect of Win 55,212-2 in rat aorta: new mechanisms involved.

R(+)-[2,3-dihydro-5-methyl-3-[(moroholinyl)methyl] pyrrolo [1,2,3-de]-1,4benzoxazinyl]-1(1-naphthalenyl) methanone mesylate (Win 55,212-2) is a synthetic cannabinoid classically classified as a potent CB(1) and CB(2) agonist with high stereoselectivity and a slight preference for CB(2) cannabinoid receptors. Its vascular actions are not always explained by its binding to these cannabinoid receptors and new targets are being proposed. The aim of this study was to further assess the vascular actions of Win 55,212-2. Isometric tension changes in response to a cumulative concentration-response curve of Win 55,212-2 (10(-9) M-10(-4) M) were recorded in aortic rings from male Wistar rats. The involvement of the endothelium, cannabinoid receptors, vanilloid receptors, and the release of calcitonin gene related peptide (CGRP) was tested. Win 55,212-2 caused a concentration-dependent vasorelaxation in rat aorta. This vascular effect was significantly inhibited by endothelial denudation, inhibition of nitric oxide synthesis, a CB(1) receptor antagonist, a transient receptor potential vanilloid-1 antagonist, capsaicin desensibilization, and a CGRP receptor antagonist (P<0.001). CB(2) and non-CB(1)/non-CB(2) receptor antagonists only caused a slight inhibitory effect in vasorelaxation to Win 55,212-2. The present findings indicate that endothelium and nitric oxide-dependent vasorelaxation induced by Win 55,212-2 mainly involves vanilloid receptors while CB(1), CB(2) and nonCB(1)/nonCB(2) cannabinoid receptors have a minor participation in its vascular effect.

The involvement of 5-HT3 and 5-HT4 receptors in two models of gastrointestinal transit in mice.

Our aim was to study the involvement of 5-hydroxytryptamine (5-HT)(3) and 5-HT(4) receptors in two models of gastrointestinal transit (GIT) in mice: the 5-hydroxytryptophan (5-HTP)-induced diarrhea and intestinal inflammation produced by an irritant agent, croton oil (CO). 5-HTP (10 mg/kg) produced diarrhea that was significantly inhibited after pretreatment with ondansetron (5-HT(3) antagonist) or RS 39604 (5-HT(4) antagonist) (1-5 mg/kg). The GIT speed was increased after CO and 5-HTP administration. 5-HT(3-4) antagonists decreased GIT after 5-HTP-treatment but not after CO-treatment. Our results show that 5-HT(3) and 5-HT(4) receptors are involved in 5-HTP-induced diarrhea. This may be the reason why 5-HT(3-4) antagonists could be useful in the treatment of carcinoid syndrome diarrhea. 5-HT(3-4) antagonists were not effective in the modifications of GIT; nevertheless, they could be useful in the treatment of inflammatory bowel diseases because some symptoms as abdominal pain, discomfort or abnormal bowel function are modulated via 5-HT(3).

New aromatic iminoimidazolidine derivatives as alpha1-adrenoceptor antagonists: a novel synthetic approach and pharmacological activity.

The design, synthesis and alpha1-adrenoceptor antagonism of a series of bis-imidazoline (1a, 2a, 3a and 4a) and bis-guanidine (1b, 2b, 3b and 4b) diphenyl derivatives are reported. All of these compounds fulfill the conditions of the most recent pharmacophore proposed for alpha1-adrenoceptors and found in the literature. Besides, a novel synthetic approach to the preparation of 2-(arylimino)imidazolidine derivatives is described. All the tested compounds, except the bis-guanidinium derivative 3b, inhibit the contractile responses induced by noradrenaline in aortic rings of rat and rabbit in a dose-dependent manner. Our results indicate that, even though some discrepancies are observed in terms of the alpha1 subtype targeted by this new family of compounds, they show an interesting profile as antagonists of alpha1-adrenoceptors and a new prototype, compound 1a, has been found deserving further development.

Decreased expression of natriuretic peptide A receptors and decreased cGMP production in the choroid plexus of spontaneously hypertensive rats.

Atrial natriuretic peptide receptor (ANP) subtypes and their signal transduction response were characterized in choroid plexus of spontaneously hypertensive (SHR) and normotensive (WKY) rats. We found two ANP receptor subtypes, guanylate cyclase coupled and uncoupled, in both rat strains. Binding of ANP was lower in SHR choroid plexus when compared to WKY. The lower ANP binding in SHR was the result of a decrease of binding to the guanylate cyclase-coupled receptor subtype A, a decrease that correlated well with the decreased ANP-induced cGMP formation in SHR. Forskolin stimulated cGMP production to the same extent in both strains. In WKY rats, ANP increased basal and forskolin-stimulated cAMP production; conversely, in SHR, ANP did not affect the basal level of cAMP and inhibited the forskolin-stimulated cAMP production. These results demonstrate differences in ANP receptor subtype expression, and ANP signal transduction in choroid plexus of hypertensive and normotensive rats, which is of possible significance to the central mechanisms of blood pressure control.

Social deprivation stress induces adaptative changes of opioid mechanisms in the rat tail artery.

Brief (7-14 days) social deprivation stress has been found to increase blood pressure in Wistar rats, an effect dependent on activation of opioid function. The role of central opioids in this and other responses to stress has been repeatedly determined, but the possible involvement of modifications of peripheral opioid mechanisms is poorly understood. To further increase this knowledge, we have examined the opioid sensitivity of tail arteries taken from social deprived Wistar rats by studying the effect of beta-endorphin and DADLE "in vitro". Both opioids inhibited the electrically-induced constriction of the preparations in a dose-dependent manner, but these actions were significantly attenuated after 7-14 days of social deprivation. When the rats were isolated for 30-35 days, the hypertensive response was still present but the arteries from group-housed and isolated animals no longer showed differential sensitivity to opioids. This difference with respect to 7-14 days of isolation could be related to age-dependent changes of opioid function, which were observed among group-housed animals. The results suggest that social deprivation stress induces an adaptation of the tail arteries to the opioid effects on contractility. It is suggested that this endogenous adaptation could be contributing to the hypertensive response observed after social deprivation.

mu- and delta-opioid receptor-mediated contractile effects on rat aortic vascular smooth muscle.

The actions of opioid receptor agonists and antagonists were studied in isolated rat aortic strips. Morphine (10(-7)-10(-6) M) had no contractile effect on resting strips but when added during the relaxation of the contractions induced by 10(-9) M noradrenaline, it induced a contractile response which was blocked by naloxone. The selective mu-opioid receptor agonist, [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO, 10(-7)-10(-6) M), induced an increase in basal tension which remained after removal of endothelium or in Ca(2+)-free solution, but was inhibited by beta-flunaltrexamine. beta-Flunaltrexamine also inhibited the contractile response induced by DAMGO added during the relaxation of the contractions induced by noradrenaline. The delta-opioid receptor agonist, [D-Pen2,D-Pen5]enkephalin, had no effect on resting tension but potentiated the contractions induced by noradrenaline; these effects were abolished by naltrindol. The selective kappa-opioid receptor agonist, bremazocine, had no effect on resting tension and did not modify the amplitude of the contractions induced by noradrenaline. These results suggest that, at low concentrations, agonists of mu- and delta-opioid receptors may act as modulators of noradrenaline-induced responses, whereas at higher concentrations, mu-opioid receptor stimulation may have a direct contractile effect in isolated rat aorta.

Vascular alterations in rats with high blood pressure induced by social deprivation stress.

While an activation of the opioid system has been found to play a role only in the triggering of the high blood pressure induced by brief (7-14 days) social deprivation stress in Wistar rats, factors responsible for the maintenance of the hypertension after long-term (30-35 days) isolation remained to be elucidated. To this aim, the effects of social deprivation stress on the functional and morphological features of blood vessels were studied. The tail artery, as a muscular vessel, and the aorta, as a large elastic vessel were used in these experiments. In ex vivo experiments, aorta and tail artery strips from rats isolated for 30-35 days were found to be hyperreactive to noradrenaline.

A modified quantitative autoradiographic assay for atrial natriuretic peptide receptors in rat brain.

New conditions for quantitative autoradiographic determination of natriuretic peptide (ANP) binding in rat brain were developed in order to inhibit hormone degradation during incubation without the use of proteinase inhibitors. This procedure includes 1-h preincubation of tissue slices in hypotonic buffer and incubation at 4 degrees C in the presence of 4% proteinase-free albumin. ANP binding to choroid plexus and subfornical organ under above conditions reached equilibrium after 90 min. ANP degradation at the end of the incubation did not exceed 2%. Binding data analysis revealed the previously undetected presence of two distinct ANP binding sites in the rat choroid plexus.

The antihypertensive agent cicletanine reverses vascular hyperreactivity to noradrenaline and cardiac hypertrophy in DOCA-salt rats.

Cicletanine, when given p.o. either acutely or subchronically, was found to produce a clear-cut antihypertensive effect in the deoxycorticosterone salt experimental rat model. This compound was able to reverse high blood pressure, even at doses deprived of diuretic effect. Subchronic treatment (30 mg/kg, p.o.; 14 days) with cicletanine reduced the enhanced contractile response to noradrenaline in deoxycorticosterone salt rat aortic strips and reversed the cardiac hypertrophy in these animals. The antihypertensive effect after long-term treatment with cicletanine in deoxycorticosterone salt rats appears to be related to an antagonism of the elevated sympathetic drive to the vascular smooth muscle.

The effect of acute and subchronic treatment with cicletanine on DOCA-salt hypertension in the rat.

Cicletanine, a new furopyridine derivative synthetized by the Institut Henri Beaufour (France) was found to work as an efficient antihypertensive agent in DOCA-salt rats. This compound also inhibited the development of cardiac hypertrophy characteristic of this sort of hypertension. The mechanism of antihypertensive action at nondiuretic doses of cicletanine remains to be studied.

Plasma catecholamines and urinary excretion of their main metabolites in three models of portal hypertension.

We have measured, by a specific radioenzymoassay, the plasma concentration of dopamine (DA) and norepinephrine (NE) and by gas chromatography the urinary excretion of some catecholamine metabolites (HVA, homovanillic acid, DOPAC, dihydroxyphenyl acetic acid; VMA, vanilmandelic acid, and DOPEG, dihydroxyphenyl glycol) in three groups of rats with portal hypertension: cirrhotic rats (CR), rats with progressive portal hypertension (PPH) and rats with progressive hepatic congestion (PHC). The three groups of rats had portal hypertension. PPH and PHC had also intrahepatic hypertension. CR rats showed an increased urinary excretion of NE and DA metabolites with a normal plasma concentration of these catecholamines, suggesting an increased turnover of NE and DA in this experimental model. PPH animals had a high plasma DA concentration with a decreased urinary excretion of catecholamine metabolites. PHC showed high plasma DA and NE levels with normal or increased urinary excretion of its metabolites. These results suggest that an increased neural activity is present in the early stages of experimental cirrhosis in rats and this alteration does not seem directly related to the portal hypertension but perhaps to the intrahepatic hypertension or to the hepatocellular damage.