Gangrena simétrica periférica vinculada a coagulación intravascular diseminada, shock séptico e infusión de noradrenalina / Symmetric peripheral gangrene linked to coagulation disseminated intravascular septic shock and infusion of noradrenaline

Introducción: Los intensivistas se enfrentan habitualmente con cuadros clínicos que pueden producir el síndrome de gangrena simétrica periférica. Al reconocer esta posibilidad, pueden prevenirlo, atenuarlo o revertirlo y reducir la morbimortalidad. Presentación del caso: Varón de 34 años con antecedentes de alcoholismo que se presenta con sepsis grave secundaria a absceso de pulmón derecho. Evolucionó con coagulación intravascular diseminada, requirió altas dosis de noradrenalina y tuvo gangrena acral en las cuatro extremidades. Finalmente falleció. Conclusiones: La combinación de shock e hipoperfusión, altas dosis de vasopresores y coagulación intravascular diseminada se vincula con la gangrena simétrica periférica que sufrió nuestro paciente. El manejo terapéutico de la gangrena simétrica periférica es multidisciplinario. (AU)

Introduction: Intensivists are confronted regularly with clinical and therapeutic conditions that can produce symmetrical peripheral gangrene syndrome. Knowing this possibility, they may prevent, attenuate and/or reverse it, and reduce its morbidity and mortality. Case presentation: A 34 years old man with history of alcoholism who presented with severe sepsis due to right lung abscess. The patient developed disseminated intravascular coagulation, he required high doses of noradrenaline infusion and he had acral gangrene in the four limbs. Finally he died. Conclusions: The combination of shock and hypoperfusion, high doses of vasopressors and disseminated intravascular coagulation is associated with the symmetrical peripheral gangrene presented by our patient. The therapeutic management of the symmetrical peripheral gangrene is multidisciplinary.(AU)

Alternatives in the induction and preparation of phenobarbital/naphthoflavone-induced S9 and their activation profiles.

With the aim of optimizing the efficiency of S9 fractions used in in vitro mutagenicity assays, different schemes for the induction of liver enzymes in rats were tried and the amount of S9 fraction required was assessed. The activity of 2-anthramine (2AA), 2-acetylaminofluorene (2AAF), 3-methylcholanthrene (3MTCL) and benzo[a]pyrene in bacterial mutagenicity tests was compared with the enzymatic activity in S9 fractions obtained from rats treated with either phenobarbital (NaPB), beta-naphthoflavone (betaNF) or combinations of both. Three pool systems prepared with different amounts of NaPB-induced S9 and betaNF-induced S9 were also analyzed for their activation capacities. Profiles of standard plate incorporation assays with Salmonella typhimurium TA98 increased with the amount of S9 fraction added for all drugs tested, except for 2AA, which showed a maximun of activity at low protein concentrations. According to these profiles, an optimal S9 protein content of 700-1000 microg/plate was estimated. For 2AAF and 3MTCL an S9 fraction obtained following a simultaneous treatment with NaPB (i.p.) and betaNF (oral gavage) (NaPB + betaNF) yielded the greatest response. This preparation was the only one which produced positive activation with 3MTCL as test drug. With the other test drugs all the S9 fractions were very active, including the NAPB + betaNF-induced S9. Both Phase I and Phase II cytochrome P450 enzymatic activities were enhanced in this S9 fraction. These results suggest that the simultaneous treatment (NaPB + betaNF) would be an adequate inducer for in vitro activation when used at 700-1000 microg protein/plate.

Site-specific effects of the nonsteroidal anti-inflammatory drug lysine clonixinate on rat brain opioid receptors.

In addition to effects in the periphery through inhibition of prostaglandin synthesis, several lines of evidence suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) act in the central nervous system. The possibility that the central action of NSAIDs involves regulation of opioid receptors was investigated by quantitative autoradiography of mu, delta, and kappa sites in rat brain slices. Increased (p < 0.05) labeling of mu receptors was observed in thalamic nuclei, gyrus dentate, and layers of the parietal cortex of rats treated for 10 days with lysine clonixinate. Labeling of delta receptors was lower in the lateral septum, and kappa sites decreased in thalamic nuclei. These effects were not mediated through direct interaction with opioid-binding sites, since receptor-binding assays using rat brain membranes confirmed that clonixinate up to 1 x 10(-4) mol/l does not inhibit mu, delta, and kappa receptor specific binding. Central effects of NSAIDs might, therefore, involve interaction with the opioid receptor system through indirect mechanisms.

Antispasmodic action of propinox on the isolated human gallbladder: possible mechanism of action.

Propinox is an antispasmodic drug frequently used in the treatment of disorders of the gastrointestinal tract, the uterus and the gallbladder, but little is known about its relaxing activity in gallbladder tissue. The main objective of this study was to determine the antispasmodic activity of propinox, compared to other antispasmodics, in the gallbladder and to assess its binding affinity to receptor sites which may be involved in its mechanism of action. Antispasmodic activity of propinox, (-) scopolamine-n-butyl bromide, atropine and verapamil was determined in human gallbladders to reduce the risk of interspecies variability. Inhibitory activities (ED50) of carbachol-induced contraction were: atropine 5.03 x 10(-8) M > propinox 1.25 x 10(-7) M > verapamil 6.63 x 10(-6) M > (-) scopolamine-n-butyl bromide 5.4 x 10(-5) M. pD'2 for propinox was 6.94, indicating non competitive inhibition of carbachol action. Radioligand binding studies were performed to determine if the antispasmodic action of the drug involved binding to muscarinic receptors or calciumantagonist sites. The inhibition constant (Ki) of propinox for muscarinic receptors of guinea pig ileum smooth muscle, which contains a mixed M2-M3 receptor population, was 1.6 x 10(-6) M. Ki for brain muscarinic receptors (M1) was 1.0 x 10(-4) M, for cardiac receptors (M2) 1.2 x 10(-6) M and from salivary gland receptors (M3) 1.5 x 10(-6) M. For binding to the dihidropiridine calcium antagonist binding sites, Ki were: 4.9 x 10(-5) M for propinox and 2.2 x 10(-7) M for verapamil. For the phenylalkylamine binding sites Ki were: 5.0 x 10(-6) M for propinox and 3.5 x 10(-8) M for verapamil. For the benzothiacepine binding sites, Ki for propinox was 5.2 x 10(-6) M. The following may be concluded: 1.--The antispasmodic activity of propinox in isolated human gallbladder was comparatively less potent than that of atropine and more potent than those of verapamil and (-) scopolamine-n-butyl bromide. 2.--Propinox showed binding to muscarinic and calcium receptors that can be related to its antispasmodic activity; suggesting that the drug is an antispasmodic with anticholinergic and musculotropic activity. 3.--The dual mechanism of action, anticholinergic and calcium-blocking, would induce synergism of pharmacodynamic effects and minimize adverse events of pure antimuscarinic drugs or calcium antagonists.

Comparison of the isolated human and guinea pig gallbladder strip models in the assessment of antispasmodic drugs.

The objective of this study was to compare the antispasmodic activities of atropine, verapamil, (-)scopolamine n-butyl bromide and propinox in the isolated human and guinea pig gallbladder strip models. Concentration-response curves for each of the agents were obtained in both models following administration of carbachol. Atropine was the only drug to show marked activity in the guinea pig gallbladder model (ED50 = 2.75 x 10(-7) M); the remaining drugs elicited less inhibition of a similar order of magnitude (ED50 = 1.65 x 10(-5), 4.18 x 10(-6) and 2.71 x 10(-5) M for verapamil, [-]scopolamine n-butyl bromide and propinox, respectively). In contrast, results obtained from the human gallbladder strip model revealed differences among the drugs (ED50 = 5.03 x 10(-8), 1.34 x 10(-6), 6.63 x 10(-6) and 5.45 x 10(-5) M for atropine, propinox, verapamil and [-]scopolamine n-butyl bromide, respectively). Based on these results, propinox showed a relative potency in the human gallbladder that was 20.22-fold higher than that in the guinea pig model followed by atropine (5.47-fold) and verapamil (2.49-fold), whereas (-)scopolamine n-butyl bromide was 0.07 times more potent in the guinea pig model. Regression analysis of ED50 values showed a lack of correlation between the two models (r = 0.44). Considering interspecies variations, further studies in human tissues are needed to evaluate the efficacy of antispasmodic drugs.

Antispasmodic action of propinox on the isolated human gallbladder: possible mechanism of action

Propinox is an antispasmodic drug frequently used in the treatment of disorders of the gastrointestinal tract, the uterus and the galbladder, but little is known about its relaxing activity in gallbladder tissue. The main objective of this study was to determine the antispasmodic activity of propinox, compared to other antispasmodics, in the gallblader and to assess its binding affinity to receptor sites which may be involved in its mechanism of action. Antispasmodic activity of propinox, (-) scopolamine-n-butyl bromide, atropine and verapamil was determined in human gallbladders to reduce the risk of interspecies variability. Inhibitory activities (ED50) of carbachol-induced contraction were: atropine 5.03x10(-8) M>propinox 1.25x10(-7) M> verapamil 6.63x10(-6)M> (-) scopolamine-n-butyl1 bromide 5.4x10(-5) M. pD'2 for propinox was 6.94, indicating non competitive inhibition of carbachol action. Radioligand binding studies were performed to determine if the antisplasmodic action of the drug involved binding to muscarinic receptors or calciumatagonist sites. The inhibition constant (Ki) of proponix for muscarinic receptors of guinea pig ileum smoth muscle, which contains a mixed M2-M3 receptor population, was 1.6x10(-6) M. Ki for brain muscarinic receptors (M1) was 1.0x10(-4) M, for cardiac receptors (M1) was 1.0x10(-4)M, for receptors (M2) 1.2x10(-6)M and from salivary gland receptors (M3) 1.5x10(-6)M. For binding to the dihidropiridine calcium antagonist binding sites, Ki were: 4.9x10(-5)M for propinox and 2.2x10(-7)M for verapamil. For the phenylakylamine binding sites Ki were: 5.0x10(-6)M for propinox and 3.5x10(-8)M for verapamil. For the benzothiacepine binding sites, Ki for propinox was 5.2x10(-6)M. The following may be concluded: 1- The antispasmodic activity of propinox in isolated human galbladder was was comparatively less potent than of atropine and more potent than those verapamil and (-) scopolamine-n-butyl bromide. 2- Propinox showed binding to muscarinic and calcium receptors that can be related to its antisplasmodic activity; suggesting that the drug is an antispasmodic with anticholinergic and musculotropic activity. 3.- The dual mechanism of action, anticholinergic and calcium-blocking, would induce synergism of pharmacodynamic effects and minimize adverse events of pure antimuscarinic drugs or calcium antagonists.

Antispasmodic action of propinox on the isolated human gallbladder: possible mechanism of action.

Propinox is an antispasmodic drug frequently used in the treatment of disorders of the gastrointestinal tract, the uterus and the gallbladder, but little is known about its relaxing activity in gallbladder tissue. The main objective of this study was to determine the antispasmodic activity of propinox, compared to other antispasmodics, in the gallbladder and to assess its binding affinity to receptor sites which may be involved in its mechanism of action. Antispasmodic activity of propinox, (-) scopolamine-n-butyl bromide, atropine and verapamil was determined in human gallbladders to reduce the risk of interspecies variability. Inhibitory activities (ED50) of carbachol-induced contraction were: atropine 5.03 x 10(-8) M > propinox 1.25 x 10(-7) M > verapamil 6.63 x 10(-6) M > (-) scopolamine-n-butyl bromide 5.4 x 10(-5) M. pD2 for propinox was 6.94, indicating non competitive inhibition of carbachol action. Radioligand binding studies were performed to determine if the antispasmodic action of the drug involved binding to muscarinic receptors or calciumantagonist sites. The inhibition constant (Ki) of propinox for muscarinic receptors of guinea pig ileum smooth muscle, which contains a mixed M2-M3 receptor population, was 1.6 x 10(-6) M. Ki for brain muscarinic receptors (M1) was 1.0 x 10(-4) M, for cardiac receptors (M2) 1.2 x 10(-6) M and from salivary gland receptors (M3) 1.5 x 10(-6) M. For binding to the dihidropiridine calcium antagonist binding sites, Ki were: 4.9 x 10(-5) M for propinox and 2.2 x 10(-7) M for verapamil. For the phenylalkylamine binding sites Ki were: 5.0 x 10(-6) M for propinox and 3.5 x 10(-8) M for verapamil. For the benzothiacepine binding sites, Ki for propinox was 5.2 x 10(-6) M. The following may be concluded: 1.--The antispasmodic activity of propinox in isolated human gallbladder was comparatively less potent than that of atropine and more potent than those of verapamil and (-) scopolamine-n-butyl bromide. 2.--Propinox showed binding to muscarinic and calcium receptors that can be related to its antispasmodic activity; suggesting that the drug is an antispasmodic with anticholinergic and musculotropic activity. 3.--The dual mechanism of action, anticholinergic and calcium-blocking, would induce synergism of pharmacodynamic effects and minimize adverse events of pure antimuscarinic drugs or calcium antagonists.

Antispasmodic action of propinox on the isolated human gallbladder: possible mechanism of action

Propinox is an antispasmodic drug frequently used in the treatment of disorders of the gastrointestinal tract, the uterus and the galbladder, but little is known about its relaxing activity in gallbladder tissue. The main objective of this study was to determine the antispasmodic activity of propinox, compared to other antispasmodics, in the gallblader and to assess its binding affinity to receptor sites which may be involved in its mechanism of action. Antispasmodic activity of propinox, (-) scopolamine-n-butyl bromide, atropine and verapamil was determined in human gallbladders to reduce the risk of interspecies variability. Inhibitory activities (ED50) of carbachol-induced contraction were: atropine 5.03x10(-8) M>propinox 1.25x10(-7) M> verapamil 6.63x10(-6)M> (-) scopolamine-n-butyl1 bromide 5.4x10(-5) M. pD2 for propinox was 6.94, indicating non competitive inhibition of carbachol action. Radioligand binding studies were performed to determine if the antisplasmodic action of the drug involved binding to muscarinic receptors or calciumatagonist sites. The inhibition constant (Ki) of proponix for muscarinic receptors of guinea pig ileum smoth muscle, which contains a mixed M2-M3 receptor population, was 1.6x10(-6) M. Ki for brain muscarinic receptors (M1) was 1.0x10(-4) M, for cardiac receptors (M1) was 1.0x10(-4)M, for receptors (M2) 1.2x10(-6)M and from salivary gland receptors (M3) 1.5x10(-6)M. For binding to the dihidropiridine calcium antagonist binding sites, Ki were: 4.9x10(-5)M for propinox and 2.2x10(-7)M for verapamil. For the phenylakylamine binding sites Ki were: 5.0x10(-6)M for propinox and 3.5x10(-8)M for verapamil. For the benzothiacepine binding sites, Ki for propinox was 5.2x10(-6)M. The following may be concluded: 1- The antispasmodic activity of propinox in isolated human galbladder was was comparatively less potent than of atropine and more potent than those verapamil and (-) scopolamine-n-butyl bromide. 2- Propinox showed binding to muscarinic and calcium receptors that can be related to its antisplasmodic activity; suggesting that the drug is an antispasmodic with anticholinergic and musculotropic activity. 3.- The dual mechanism of action, anticholinergic and calcium-blocking, would induce synergism of pharmacodynamic effects and minimize adverse events of pure antimuscarinic drugs or calcium antagonists. (AU)

Actividad bactericida de los neutrofilos en pacientes con infecciones graves y moderadas. / Bactericidal activity of neutrophils in patients with severe and moderate infections

Se estudio la funcion bactericida de los neutrofilos en 20 pacientes con sepsis grave, 9 con infecciones moderadas y 17 voluntarios sanos.La actividad bactericida se midio mediante la prueba de reduccion del azul de nitrotetrazolio (NBT), utilizando uma tecnica estimulada por Staphylococcus epidermidis y cuantificable colorimetricamente. Los resultados revelaron que ambos grupos de pacientes diferian significativamente del grupo control (p < 0.01) Los datos expuestos demostraron una inhibicion de la respuesta neutrofila en la sepsis severa, que contrasta con los valores altos de reduccion del NBT hallados en los procesos infecciosos de menor gravedad Esta disminuicion en la capacidad bactericida de los neutrofilos hallada en pacientes septicos a pesar de la estimulacion y descartada una disfuncion hereditaria del sistema fagocitario puede considerarse un defecto adquirido producido posiblemente por el mismo proceso septico