Eventos Críticos en el Recién Nacido / Newborn Critical Events

El periodo neonatal corresponde a una etapa en el desarrollo en el que las convulsiones constituyen la expresión clínica de disfunción del sistema nervioso central. Estas se manifiestan por una alteración en la función neurológica que puede ser motora, autonómica, de la conducta o una combinación de ellas. Dado que en este periodo el desarrollo anatómico, bioquímico y fisiológico, presentan características muy diferentes al desarrollo del niño mayor, las convulsiones pueden ser muy difíciles de identificar y pueden confundirse con eventos clínicos paroxísticos no epilépticos del recién nacido. Lo anterior se explica porque las convulsiones presentan patrones poco organizados, suelen no ser bien definidas y el registro electroencefalográfico es diferente al del niño mayor. En su mayoría las CN son secundarias a una etiología específica, por lo que es indispensable encontrar la causa lo cual se encuentra fuertemente relacionado al pronóstico. También es necesario diferenciar los eventos no epilépticos, para un óptimo manejo. Palabras clave: convulsiones neonatales, newborn, seizures, non epileptic seizures, disfunción cerebral.

The neonatal period corresponds to a developmental stage in which seizures are the clinical expression of central nervous system dysfunction. These are manifested by a change in neurological function that can be motor, autonomic, behavior or a combination of them.Given that in this period the anatomical, biochemical and physiological development present with very different characteristics to those of the older child, seizures can be very difficult to identify, and can be confused with paroxysmal non epileptic clinical events of the newborn. This is explains why seizures have little organized patterns are often not well defined and the Electroencephalographic record is different from that found in the older child. For the most part, neonatal seizures are secondary to a specific etiology, so it is essential to find the cause, which is strongly related to the prognosis. It is also necessary to differentiate non-epileptic events, for optimal handling. Key words: Neonatal seizures, neonatal, non epileptic seizures, brain dysfunction.

Improving potency and selectivity of a new class of non-Zn-chelating MMP-13 inhibitors.

Discovery and optimization of potency and selectivity of a non-Zn-chelating MMP-13 inhibitor with the aid of protein co-crystal structural information is reported. This inhibitor was observed to have a binding mode distinct from previously published MMP-13 inhibitors. Potency and selectivity were improved by extending the hit structure out from the active site into the S1' pocket.

[TIVA-TCI (Total IntraVenous Anesthesia-Target Controlled Infusion) versus isoflurane anesthesia for laparoscopic cholecystectomy. Postoperative nausea and vomiting, and patient satisfaction]. / TIVA-tCI vs. anestezia inhalatorie pentru colecistectomia laparoscopica. Incidenta sindromului emetic postoperator si satisfactia pacientilor.

UNLABELLED: Numerous studies have shown that TIVA is followed by a significant reduction in the incidence of PONV in day-case surgery, including laparoscopic cholecystectomy, where the incidence of PONV can reach 70% according to some studies. TCI is the TIVA technique that maintain a constant plasma concentration due to pharmacokynetic models incorporated in TCI device that inject the anesthetic agent. Besides implementing TIVA-TCI in clinical practice in Romania, our study was designed to evaluate the impact of TIVA-TCI on postoperative outcome and our patient satisfaction after laparoscopic cholecystectomy. PATIENTS AND METHODS: After informed consent, 70 patients ASAI/II undergoing laparoscopic cholecystectomy were randomized in 2 equal study groups: group 1 (n = 35) included patients with TIVA-TCI with propofol (Cpi = 4 microg/ml) and remifentanil, and group 2 (n = 35) were patients undergoing Isoflurane anesthesia. In both groups propofol was administered during induction and remifentanil followed the same protocol: 0.5 microg/kg/min in the first minute during induction, followed by 0.25 microg/kg/min. This infusion was modified by 0.05 microg/kg/min steps according to analgesic needs. PONV (evaluated as both incidence and number of episodes), severity of pain and patient satisfaction score IOWA were compared between study groups. RESULTS: Both the incidence of PONV (p = 0.03) and the number of episodes/24 h/patients (p = 0.01) were significantly lower in TIVA-TCI group, while there was no significant difference in opioid requirements in study groups (p = 0.21). Patients IOWA satisfaction score at 24 hours postoperatively was significantly higher in TIVA-TCI groups (p = 0.0001). CONCLUSIONS: Compared with Isoflurane, TIVA-TCI was followed by significantly lower incidence of PONV and significantly greater patients satisfaction.

Síndrome de Ramsay-Himt en Pediatría: reporte de cuatro casos y revisión de la literatura / Ramsay Hunt syndrome in children: four cases and review

Ramsay-Hunt Syndrome (RHS) is a rare affection characterized by peripheral facial paralysis (PFP), skin eruption in the auricular canal and cochleovestibular symptoms. It is produced by varicella-zoster virus (VZV) reactivation at the geniculate ganglia. We report four patients between 3 and 17 years-old with RHS. Earache was the first symptom in two cases and three had cochleovestibular compromise. The direct immunofluorescence from the vesicular lesión was positive for VZV in two of them. All patients received treatment with aeyelovir and in three cases, this was associated with steroids. Three children had complete resolution of the PFP. RHS is an infrequent disease in the pediatric population and it should be suspected in children with PFP, erythema, vesicles and/or auricular pain. Early treatment with aeyelovir therapy could improve the recovery rate of facial nerve palsy.

El síndrome de Ramsay-Hunt (SRH) corresponde a una inusual afección caracterizada por parálisis facial periférica (PFP), erupción en el pabellón auricular ipsilateral y compromiso cocleo-vestibular. Es producida por reactivación del virus varicela zoster (VVZ) a nivel del ganglio geniculado. Se reporta una serie de cuatro pacientes entre 3 y 17 años de edad con SRH. La otalgia fue el primer síntoma en dos casos, tres de ellos presentaron sintomatología vestibular periférica y uno déficit cócleo-vestibular. La inmunofluorescencia directa de hisopado de lesión vesicular fue positiva para VVZ en dos niños. Todos recibieron tratamiento con aciclovir y tres recibieron además corticoesteroides. Tres niños tuvieron recuperación clínica completa. El SRH es una entidad poco frecuente en pediatría y debe sospecharse en niños con PFP, eritema, vesículas y/o dolor auricular, ya que el tratamiento precoz con aciclovir pudiera mejorar la evolución de la PFP.

[Ramsay Hunt syndrome in children: four cases and review]. / Síndrome de Ramsay-Himt en pediatría: reporte de cuatro casos y revisión de la literatura.

Ramsay-Hunt Syndrome (RHS) is a rare affection characterized by peripheral facial paralysis (PFP), skin eruption in the auricular canal and cochleovestibular symptoms. It is produced by varicella-zoster virus (VZV) reactivation at the geniculate ganglia. We report four patients between 3 and 17 years-old with RHS. Earache was the first symptom in two cases and three had cochleovestibular compromise. The direct immunofluorescence from the vesicular lesion was positive for VZV in two of them. All patients received treatment with aeyelovir and in three cases, this was associated with steroids. Three children had complete resolution of the PFP. RHS is an infrequent disease in the pediatric population and it should be suspected in children with PFP, erythema, vesicles and/or auricular pain. Early treatment with aeyelovir therapy could improve the recovery rate of facial nerve palsy.

A steric antagonism of actin polymerization by a salmonella virulence protein.

Salmonella spp. require the ADP-ribosyltransferase activity of the SpvB protein for intracellular growth and systemic virulence. SpvB covalently modifies actin, causing cytoskeletal disruption and apoptosis. We report here the crystal structure of the catalytic domain of SpvB, and we show by mass spectrometric analysis that SpvB modifies actin at Arg177, inhibiting its ATPase activity. We also describe two crystal structures of SpvB-modified, polymerization-deficient actin. These structures reveal that ADP-ribosylation does not lead to dramatic conformational changes in actin, suggesting a model in which this large family of toxins inhibits actin polymerization primarily through steric disruption of intrafilament contacts.

Structural evidence for feedback activation by Ras.GTP of the Ras-specific nucleotide exchange factor SOS.

Growth factor receptors activate Ras by recruiting the nucleotide exchange factor son of sevenless (SOS) to the cell membrane, thereby triggering the production of GTP-loaded Ras. Crystallographic analyses of Ras bound to the catalytic module of SOS have led to the unexpected discovery of a highly conserved Ras binding site on SOS that is located distal to the active site and is specific for Ras.GTP. The crystal structures suggest that Ras.GTP stabilizes the active site of SOS allosterically, and we show that Ras.GTP forms ternary complexes with SOS(cat) in solution and increases significantly the rate of SOS(cat)-stimulated nucleotide release from Ras. These results demonstrate the existence of a positive feedback mechanism for the spatial and temporal regulation of Ras.

Tramadol added to lidocaine for intravenous regional anesthesia.

UNLABELLED: Sixty volunteers, divided into four groups of 15 each, received IV regional anesthesia of the upper limb with 40 mL tramadol 0.25%, sodium chloride 0.9%, lidocaine 0.5%, or 100 mg tramadol-containing lidocaine 0.5%. By using a double-blinded method, we tested the onset and recovery of sensory block at six sites of the forearm and hand as well as onset of complete motor block. The symptoms after deflation of the tourniquet were recorded. The onset and recovery of sensory block and the onset of motor block were similar in the tramadol and saline groups. However, in the Tramadol-Lidocaine Group, the speed of onset of sensory block was faster than in the Lidocaine Group. In the Tramadol and the Tramadol-Lidocaine Groups, the incidence of skin rash and painful or burning sensation at the injection site was increased. We conclude that tramadol 0.25% does not have a local anesthetic effect when used as a sole drug for IV regional anesthesia, but might modify the action of local anesthetic, providing a shorter onset time of sensory block. IMPLICATIONS: Tramadol, a centrally acting analgesic, might have local anesthetic properties, as do some opioid drugs. We demonstrated that 0.25% tramadol solution containing 100 mg tramadol is not effective as a sole drug, but may improve the action of 0.5% lidocaine for intravenous regional anesthesia. The increased incidence of side effects may limit the clinical use of tramadol.

The structural basis of the activation of Ras by Sos.

The crystal structure of human H-Ras complexed with the Ras guanine-nucleotide-exchange-factor region of the Son of sevenless (Sos) protein has been determined at 2.8 A resolution. The normally tight interaction of nucleotides with Ras is disrupted by Sos in two ways. First, the insertion into Ras of an alpha-helix from Sos results in the displacement of the Switch 1 region of Ras, opening up the nucleotide-binding site. Second, side chains presented by this helix and by a distorted conformation of the Switch 2 region of Ras alter the chemical environment of the binding site for the phosphate groups of the nucleotide and the associated magnesium ion, so that their binding is no longer favoured. Sos does not impede the binding sites for the base and the ribose of GTP or GDP, so the Ras-Sos complex adopts a structure that allows nucleotide release and rebinding.

Regulation of Sos activity by intramolecular interactions.

The guanine nucleotide exchange factor Sos mediates the coupling of receptor tyrosine kinases to Ras activation. To investigate the mechanisms that control Sos activity, we have analyzed the contribution of various domains to its catalytic activity. Using human Sos1 (hSos1) truncation mutants, we show that Sos proteins lacking either the amino or the carboxyl terminus domain, or both, display a guanine nucleotide exchange activity that is significantly higher compared with that of the full-length protein. These results demonstrate that both the amino and the carboxyl terminus domains of Sos are involved in the negative regulation of its catalytic activity. Furthermore, in vitro Ras binding experiments suggest that the amino and carboxyl terminus domains exert negative allosteric control on the interaction of the Sos catalytic domain with Ras. The guanine nucleotide exchange activity of hSos1 was not augmented by growth factor stimulation, indicating that Sos activity is constitutively maintained in a downregulated state. Deletion of both the amino and the carboxyl terminus domains was sufficient to activate the transforming potential of Sos. These findings suggest a novel negative regulatory role for the amino terminus domain of Sos and indicate a cooperation between the amino and the carboxyl terminus domains in the regulation of Sos activity.

Mutation of Pro-258 in transmembrane domain 6 constitutively activates the G protein-coupled alpha-factor receptor.

The alpha-factor pheromone receptor stimulates MATa yeast cells to undergo conjugation. The receptor contains seven transmembrane domains that function in ligand binding and in transducing a signal to the cytoplasmic receptor sequences to mediate G protein activation. A genetic screen was used to isolate receptor mutations that constitutively signal in the absence of alpha-factor. The Pro-258-->Leu (P258L) mutation caused constitutive receptor signaling that was equivalent to about 45% of the maximum level observed in wild-type cells stimulated with alpha-factor. Mutations of both Pro-258 and the adjacent Ser-259 to Leu increased constitutive signaling to > or = 90% of the maximum level. Since Pro-258 occurs in the central portion of transmembrane domain 6, and since proline residues are expected to cause a kink in alpha-helical domains, the P258L mutation is predicted to alter the structure of transmembrane domain 6. The P258L mutation did not result in a global distortion of receptor structure because alpha-factor bound to the mutant receptors with high affinity and induced even higher levels of signaling. These results suggest that sequences surrounding Pro-258 may be involved in ligand activation of the receptor. Conformational changes in transmembrane domain 6 may effect a change in the adjacent sequences in the third intracellular loop that are thought to function in G protein activation. Greater than 90% of all G protein-coupled receptors contain a proline residue at a similar position in transmembrane domain 6, suggesting that this aspect of receptor activation may be conserved in other receptors.