Sobre la reproducibilidad y la efectividad del APACHE II, el APACHE III adaptado para España y el SAPS II en 9 unidades de cuidados intensivos en España / On reproducibility and effectiveness of APACHE II, APACHE III adapted for Spain and SAPS II in 9 intensive care units in Spain

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[Jejunal mucormycosis in a patient with Hodgkin's lymphoma]. / Mucormicosis yeyunal en paciente con linfoma de Hodgkin.

We report a case of intestinal mucormycosis in a 46-year-old male diagnosed with classical Hodgkin's disease, IV-B stage. During the first phase of chemotherapy he had a massive digestive bleeding event secondary to a jejunal ulcer, and zygomicosis mucor-type was diagnosed by endoscopic biopsy. The patient was treated with antifungal drugs and surgical resection of the intestine involved. At surgery a double covered perforation of the jejunum was seen. Pathological examination confirmed the previous diagnosis. After one year of follow-up the patient is doing well, and his lymphoma is on remission. To our best knowledge this is the second case of intestinal mucormycosis in a patient with Hodgkin's lymphoma reported in the medical literature.

Mucormicosis yeyunal en paciente con linfoma de Hodgkin / No disponible

Comunicamos un caso de mucormicosis intestinal en un hombrede 46 años de edad, diagnosticado de enfermedad de Hodgkinclásica, estadio IV-B. Durante la primera fase de la quimioterapia,sufrió una hemorragia digestiva masiva secundaria a unaúlcera yeyunal por zigomicosis tipo mucor, diagnosticada porbiopsia endoscópica. El paciente fue tratado con antifúngicos yresección quirúrgica del intestino afectado. En la cirugía, se aprecióuna doble perforación yeyunal cubierta. El estudio anatomopatológicode la pieza confirmó el diagnóstico previo. Tras un añode seguimiento, el paciente está recuperado y su linfoma deHodgkin en remisión completa. Tras una extensa revisión de la literatura,según nuestro conocimiento, este es el segundo caso publicadoen la literatura de mucormicosis intestinal en un pacientecon linfoma de Hodgkin

We report a case of intestinal mucormycosis in a 46-year-oldmale diagnosed with classical Hodgkin’s disease, IV-B stage. Duringthe first phase of chemotherapy he had a massive digestivebleeding event secondary to a jejunal ulcer, and zygomicosis mucor-type was diagnosed by endoscopic biopsy. The patient wastreated with antifungal drugs and surgical resection of the intestineinvolved. At surgery a double covered perforation of the jejunumwas seen. Pathological examination confirmed the previous diagnosis.After one year of follow-up the patient is doing well, andhis lymphoma is on remission. To our best knowledge this is thesecond case of intestinal mucormycosis in a patient with Hodgkin’slymphoma reported in the medical literature

[Mortality and hospital stay adjusted for severity as indicators of effectiveness and efficiency of attention to intensive care unit patients]. / Mortalidad y estancia hospitalaria ajustada por gravedad como indicadores de efectividad y eficiencia de la atención de pacientes en Unidades de Cuidados Intensivos.

OBJECTIVE: To evaluate effectiveness and efficiency of ICU care using the APACHE III model customized for Spain. DESIGN: Prospective, observational, multi-centre cohort study. SETTING: Nine Spanish ICUs. PATIENTS: One thousand two hundred and eleven patients admitted consecutively. Patients under 16 years of age, patients admitted for less than 24 hours, patients admitted for definitive pacemaker implant and ICU readmissions within the same hospital stay were excluded. PRIMARY ENDPOINTS: All the necessary endpoints to calculate the APACHE III score and predicted mortality risk were collected. The Standardized Mortality Ratio (SMR) was calculated. The Actual Weighted Hospital Days (AWHD) was calculated according to the patient's status and patient's location (ward or ICU). The Weighted Hospital Days Predicted (WHDP) was calculated according to the multiple regression model that provided the best explanation of the hospital stay. Later, the Standardized Resource Use Performance Index (SRUPI), computed as AWHD/WHDP, was calculated for each hospital. RESULTS: The SMR was 0.9 (95% CI: 0.82-0.99), SRUPI was greater than 1 in 3 of 9 hospitals, According the SMR and SRUPI only one hospital was qualified as an outlier. CONCLUSIONS; In this study, no relationship was found between quality of care and use of resources. Moreover, this methodology may be a useful tool in order to detect deviations from the standard of care and use of resources, and in this way to lead to the analysis of different causes, the differences among hospitals being taken into account.

[Evaluation of the reproducibility of the data collection for the APACHE II, APACHE III adapted for Spain and the SAPS II in nine intensive care units in Spain]. / Evaluación de la reproducibilidad de la recogida de datos para el APACHE II, APACHE III adaptado para España y SAPS II en 9 Unidades de Cuidados Intensivos en España.

OBJECTIVE: To assess reproducibility in data collection and its influence on the calculation of the severity scoring and mortality risk in APACHE II, APACHE III adapted for Spain and SAPS II. DESIGN: Multicenter, prospective, observational cohort study. SETTING: Nine Spanish Intensive Care Units (ICUs). PATIENTS: 1,211 consecutive patients admitted during the study period were included. Those patients under 16 years of age, those with a stay in the ICU of less than 24 hours, those admitted for scheduled pacemaker implant and those readmitted to the ICU within the same hospital admission were excluded. INTERVENTION: None. ENDPOINTS OF INTEREST: The data needed to calculate the severity and mortality risk scores were collected. A total of 10% of the patients were chosen by simple random sampling and the same data were collected by an independent group of intensive care physicians. Finally, the data obtained by the two groups of intensivists were compared. RESULTS: Significant differences were detected in the acute physiology score (APS) and severity score used for the calculation of APACHE III and SAPS II, and the predicted risk of death calculated for SAPS II. The percentage of agreement on admission diagnosis to the ICU was 50% for both APACHE II and III models. Nonetheless, in most of the patients (76.58% for APACHE II and 79.82% for APACHE III), the difference in the predicted risk of death due to the different assignation of diagnoses on admission to the ICU was less than 10%. CONCLUSIONS: In this study, APS was the most influential factor on the reproducibility of severity scores and risk of death prediction. Admission diagnosis assignment had no significant impact on the reproducibility of the predicted mortality risk.

Mortalidad y estancia hospitalaria ajustada por gravedad como indicadores de efectividad y eficiencia de la atención de pacientes en Unidades de Cuidados Intensivos / Mortality and hospital stay adjusted for severity as indicators of effectiveness and efficiency of attention to Intensive Care Unit patients

Objetivo. Evaluar la efectividad y la eficiencia de la atención en Unidadesa de Cuidados Intensivos (UCI) mediante el índice APACHE III adaptado a España. Diseño. Estudio multicéntrico prospectivo observacional de cohortes. Ámbito. Nueve UCI en España. Pacientes. Mil doscientos once pacientes ingresados consecutivamente. Se excluyeron menores de 16 años, con estancia inferior a 24 horas, ingresados para implante definitivo de marcapasos y reingresados en UCI dentro del mismo ingreso hospitalario. Variables de interés principales. Se recogieron para cada paciente los datos de filiación y todas aquellas variables necesarias para calcular el índice APACHE III y su riesgo de mortalidad. Se calculó la razón estandarizada de mortalidad (REM). Se calculó la estancia hospitalaria ponderada observada (EHPO) adjudicando diferentes pesos a cada día de estancia, en función del tipo de paciente y del lugar de cada día de estancia. Se calculó la estancia hospitalaria ponderada predicha (EHPP) según el modelo de regresión múltiple que mejor explicaba la estancia hospitalaria. Posteriormente se calculó el índice de utilización de recursos (IUR) ­ EHPO/EHPP ­ para cada hospital. Resultados. La REM global fue de 0,9 (IC 95%: 0,82-0,99). El IUR fue mayor de 1 en tres de los 9 hospitales. Valorando el REM y el IUR conjuntamente sólo un hospital se salió del estándar marcado por los 9 hospitales del estudio. Conclusiones. En este estudio no se encontró relación entre la calidad de la asistencia a los pacientes y la utilización de recursos; sin embargo esta metodología puede ser una herramienta para detectar desviaciones del estándar por exceso de la mortalidad o de la utilización de recursos, y esto, conducir al análisis de posibles causas, teniendo en cuenta las diferencias entre los distintos hospitales y UCI

Objective. To evaluate effectiveness and efficiency of ICU care using the APACHE III model customized for Spain. Desing. Prospective, observational, multi-centre cohort study. Setting. Nine Spanish ICUs. Patients. One thousand two hundred and eleven patients admitted consecutively. Patients under 16 years of age, patients admitted for less than 24 hours, patients admitted for definitive pacemaker implant and ICU readmissions within the same hospital stay were excluded. Primary endpoints. All the necessary endpoints to calculate the APACHE III score and predicted mortality risk were collected. The Standardized Mortality Ratio (SMR) was calculated. The Actual Weighted Hospital Days (AWHD) was calculated according to the patient's status and patient's location (ward or ICU). The Weighted Hospital Days Predicted (WHDP) was calculated according to the multiple regression model that provided the best explanation of the hospital stay. Later, the Standardized Resource Use Performance Index (SRUPI), computed as AWHD/WHDP, was calculated for each hospital. Results. The SMR was 0.9 (95% CI: 0.82-0.99), SRUPI was greater than 1 in 3 of 9 hospitals, According the SMR and SRUPI only one hospital was qualified as an outlier. Conclusions. In this study, no relationship was found between quality of care and use of resources. Moreover, this methodology may be a useful tool in order to detect deviations from the standard of care and use of resources, and in this way to lead to the analysis of different causes, the differences among hospitals being taken into account

Evaluación de la reproducibilidad de la recogida de datos para el APACHE II, APACHE III adaptado para España y SAPS II en 9 Unidades de Cuidados Intensivos en España / Evaluation of the reproducibility of the data collection for the APACHE II, APACHE III adapted for Spain and the SAPS II in nine Intensive Care Units in Spain

Objetivo. Evaluar la reproducibilidad en la recogida de datos y su influencia en el cálculo de la gravedad y del riesgo predicho de muerte para los modelos APACHE II, APACHE III adaptado para España y SAPS II. Diseño. Estudio multicéntrico, prospectivo y observacional de cohortes. Ámbito. Nueve Unidades de Cuidados Intensivos (UCI) en España. Pacientes. Inclusión consecutiva de los pacientes ingresados en el período de estudio. Se excluyeron los pacientes menores de 16 años, con estancia en UCI menor de 24 horas, los ingresados para implante programado de marcapasos y los reingresados en UCI dentro del mismo ingreso hospitalario. Intervención. Ninguna. Variables de interés principales. Se recogieron los datos necesarios para el cálculo de las puntuaciones de gravedad y del riesgo predicho de muerte. Se seleccionaron el 10% de los pacientes por muestreo aleatorio simple y se recogieron los mismos datos por un grupo independiente de intensivistas. Finalmente se compararon los datos recogidos por los dos grupos de intensivistas. Resultados. Se encontraron diferencias significativas en el APS (acute physiology score) y puntuación de gravedad calculados para el APACHE III y SAPS II, y en el riesgo de muerte predicho por SAPS II. El porcentaje de acuerdos en el diagnóstico de ingreso en UCI fue del 50% para los modelos APACHE II y III. En la mayoría de los pacientes (76,58% en el APACHE II y 79,82% en el APACHE III) la diferencia en el riesgo predicho de muerte debido a la diferente asignación del diagnóstico de ingreso en UCI fue menor del 10%. Conclusiones. En este estudio el APS se mostró como el factor más influyente en la reproducibilidad de los índices de gravedad y del cálculo del riesgo predicho de muerte. El diagnóstico de ingreso en UCI no mostró un impacto importante en la reproducibilidad del riesgo predicho de muerte

Objective. To assess reproducibility in data collection and its influence on the calculation of the severity scoring and mortality risk in APACHE II, APACHE III adapted for Spain and SAPS II. Design. Multicenter, prospective, observational cohort study. Setting. Nine Spanish Intensive Care Units (ICUs). Patients. 1,211 consecutive patients admitted during the study period were included. Those patients under 16 years of age, those with a stay in the ICU of less than 24 hours, those admitted for scheduled pacemaker implant and those readmitted to the ICU within the same hospital admission were excluded. Intervention. None. Endpoints of interest. The data needed to calculate the severity and mortality risk scores were collected. A total of 10% of the patients were chosen by simple random sampling and the same data were collected by an independent group of intensive care physicians. Finally, the data obtained by the two groups of intensivists were compared. Results. Significant differences were detected in the acute physiology score (APS) and severity score used for the calculation of APACHE III and SAPS II, and the predicted risk of death calculated for SAPS II. The percentage of agreement on admission diagnosis to the ICU was 50% for both APACHE II and III models. Nonetheless, in most of the patients (76.58% for APACHE II and 79.82% for APACHE III), the difference in the predicted risk of death due to the different assignation of diagnoses on admission to the ICU was less than 10%. Conclusions. In this study, APS was the most influential factor on the reproducibility of severity scores and risk of death prediction. Admission diagnosis assignment had no significant impact on the reproducibility of the predicted mortality risk

Hemispheric laterality and dissociative tendencies: differences in emotional processing in a dichotic listening task.

The present work investigates whether the hemispheric processing of both verbal and emotional stimuli, studied by means of a dichotic listening task, differs between normal high and low dissociators as assessed by the Dissociative Experiences Scale (DES; Bernstein & Putnam (1986). Development, reliability and validity of a dissociation scale. Journal of Nervous and Mental Disease, 174(2), 727-735). Two groups of subjects (50 high and 50 low dissociators), participated in the experiment. The task consisted in identifying both verbal and emotional stimulus-targets, respectively, on successive sessions. Reaction time and response accuracy were registered and analysed using ANOVA (Analysis of Variance). The interaction between stimuli (verbal, emotional), channel (right ear, left ear), and dissociation level (high, low) reached statistical significance in terms of accuracy measures (d': F(1,98)=4.75; p<.05). Both high and low dissociators exhibited the expected right ear advantage (REA effect) on verbal targets. On the other hand, whereas low dissociators exhibited the expected left ear advantage (LEA effect) on emotional targets, high dissociators failed to follow this typical pattern of hemispheric asymmetry: both hemispheres exhibited similar performances. These results confirm the hypothesis that dissociation is related to changes in hemispheric processing, specifically of emotional information.

Molecular and cellular mechanisms in the pathophysiology of severe head injury.

The pathophysiological process following traumatic brain injury is extremely complex and not fully understood. Recent developments have further advanced our knowledge of the cellular and molecular mechanisms that cause this damage. The excitotoxic damage, alterations in calcium homeostasis and free radical induced damage are thought to be the key pathways in this process. It is believed that the final target of all these pathways is the mitochondria, through the alteration in the mitochondrial permeability transition pore. Moreover, the inflammatory response may be important in the exacerbation of secondary damage but its exact role is not very well known. Further advances in our understanding of the cellular and molecular mechanisms will be crucial in the design of new therapies that should improve the prognosis of the traumatic brain injury patients.

Mitogen-induced p53 downregulation precedes vascular smooth muscle cell migration from healthy tunica media and proliferation.

The tumor suppressor protein p53 plays an important role in the cell-cycle G(1) and G(2) checkpoints. In response to DNA damage, p53 can induce the transcription of p21, which inhibits the activation of various G(1) cyclin/cyclin-dependent kinase complexes. It is not known whether p53 plays a role in the initial migration of vascular smooth muscle cells from the arterial tunica media (mVSMCs). In this study, we have investigated whether mVSMC migration from healthy tunica media of young pigs and proliferation are regulated by p53. After 6 hours of incubation in mitogen-rich medium, explanted porcine tunica media tissue showed complete downregulation of p53 protein and p53 mRNA. The blockage of gene activity was not due to DNA methylation at the 5' control region of the gene. The mVSMC outgrowth did not show p53 expression. Mitogen-depletion of cultured p53(-)/mVSMCs did not restore p53 expression. Incubation of explanted porcine tunica media tissue in mitogen-deprived medium increased p53 protein content and blocked mVSMC outgrowth from the explant. As in p53-deficient rodent cells, mVSMCs incubated with colcemid overrode the spindle-dependent checkpoint, giving polyploidy and chromosomal pairing. UV-induced DNA damage in mVSMCs incubated with mitogen-free medium induced p53 expression and apoptotic cell death showing DNA nucleosomal laddering. However, UV-irradiated mVSMCs incubated in mitogen-rich medium did not express p53 and did not show cell death. In conclusion, our results demonstrate that early mVSMC migration from the tunica media requires mitogen-induced suppression of p53 that is highly expressed in contractile mVSMCs residing in the healthy vessel wall.

Estudio Delphi de la Sociedad Valenciana de Cirugía: tratamiento quirúrgico del cáncer gástrico / A Delphi study by the Surgical Society of Valencia, Spain: surgical treatment of gastric cancer

Se presentan los resultados del primer estudio de consenso auspiciado por la Sociedad Valenciana de Cirugía sobre el tratamiento quirúrgico del cáncer gástrico. Se trata de un esudio tipo Delphi, con la participación de 31 expertos pertenecientes a la mayoría de hospitales de la Comunidad Valenciana. Los temas consensuados han versado sobre los siguientes aspectos: nutrición artificial, métodos de estadificación preoperatoria, tipo de resección y de linfadenectomía, técnicas de reconstrucción, criterios de resecabilidad y temas de organización (AU)

The effect of cyclic adenosine monophosphate on the mitogen-activated protein kinase pathway depends on both the cell type and the type of tyrosine kinase-receptor.

The mitogen-activated protein kinase (MAP kinase) is a key participant in growth factor-stimulated intracellular events such as proliferation and differentiation. We and others have previously described a cross-talk between the MAP kinase pathway and the cAMP pathway. Indeed, in several cell lines and, in particular in fibroblasts, an increase in the level of cAMP produced an inhibition of MAP kinase together with decreased cell proliferation. In contrast, in PC12 cells, cAMP induced an increase in the NGF-induced activation of MAP kinase concomitantly with augmented NGF-induced differentiation. Therefore, it has been proposed that the cellular context is important for the nature of the cAMP effects on growth factor-stimulated MAP kinase activity. Here we show that the type of tyrosine kinase receptor stimulated also participates in the nature of the cAMP effect. Thus, in NIH3T3 fibroblasts expressing NGF receptors (NIH3T3/trk cells) we found that cAMP potentiates NGF-stimulated ERK1 and MEK1 activities, whereas in NIH3T3 fibroblasts expressing insulin receptors (NIH3T3/IR cells) we saw no effect of cAMP on the activation of insulin-stimulated ERK1 and MEK1. In PC12 cells and in Rat1 fibroblasts expressing insulin receptors (PC12/IR and Rat1/IR cells) we observed, respectively, a potentiation and an inhibition of insulin-stimulated ERK1 activity. In addition, cAMP does not seem to modify the basal nor growth factor-stimulated She or IRS-1 tyrosine phosphorylation in the different cell lines studied. Finally, we observed that cAMP inhibited serum- and insulin-induced, but not NGF-induced, cell proliferation in NIH3T3 cells. However, cAMP potentiated insulin-stimulated cell differentiation in PC12/IR cells. These results led us to conclude that the cAMP effect on cell proliferation in NIH3T3 fibroblasts and PC12/IR cells appears to be correlated, in part, with the effect of cAMP on the MAP kinase pathway, but by itself this pathway cannot fully account for these observations.

Larch arabinogalactan for hepatic drug delivery: isolation and characterization of a 9 kDa arabinogalactan fragment.

Purified arabinogalactan [AG(37 kDa)] from Larix occidentalis is composed of repeating units of similar molecular weight and composition. A 9 kDa arabinogalactan [AG(9 kDa)] has been obtained in high yield from AG(37 kDa) either by autoclaving at 121 degrees C or by exposure to alkaline solution in the presence of sodium borohydride. The weight average molecular weight of AG(37 (kDa) was determined to be 37 and 38 kDa by intensity light scattering and sedimentation equilibrium, respectively. The weight average molecular weight of AG(9 kDa) was determined to be 9.1 and 9.5 kDa by intensity light scattering and sedimentation equilibrium, respectively. MALDI-TOF mass spectrometry yielded a molecular weight at the peak of the distribution of 8.3 kDa for AG(9 kDa). Both AG(37 kDa) and AG(9 kDa) exhibited narrow molecular-weight distributions (Mw/Mn approximately 1.2). AG(37 kDa) and AG(9 kDa) exhibit nearly identical 13C-NMR spectra, monosaccharide composition, and sugar linkages. It is proposed that AG(37 kDa) is composed of covalently bound subunits of AG(9 kDa). AG(37 kDa) and AG(9 kDa) bind isolated hepatocyte asialoglycoprotein receptor equally well. As a result AG(9 kDa) is a candidate for use in hepatocyte directed drug delivery and may be more desirable for such use than is AG(37 kDa).

Conjugation of adenine arabinoside 5'-monophosphate to arabinogalactan: synthesis, characterization, and antiviral activity.

A conjugate consisting of the antiviral nucleotide analogue adenine arabinoside 5'-monophosphate (araAMP, vidarabine monophosphate) and the naturally occurring polysaccharide arabinogalactan was synthesized. The conjugate consisted of 7.9 araAMP residues per molecule of arabinogalactan. The proposed structure of the conjugate was consistent with 13C NMR spectroscopic studies. Daily injections of the conjugate, at a dose of 3 mg of araAMP/kg, into woodchuck carriers of woodchuck hepatitis virus (WHV) decreased serum levels of WHV DNA. A dose of 3 mg/kg of unconjugated araAMP was ineffective, while a higher dose of araAMP (15 mg/kg, 14 days) produced a drop in WHV DNA. After cessation of dosing with the conjugate, serum viral DNA levels remained depressed for 42 days. In contrast, after cessation of dosing with araAMP, WHV DNA rapidly returned to original levels.

Arabinogalactan for hepatic drug delivery.

Arabinogalactan, a polysaccharide from the tree Larix occidentalis, has been purified and its biological and physical properties described. Intravenous injection of radiolabeled arabinogalactan (4 mg/kg) in rats resulted in 52.5% of the dose being present in the liver, while prior injection of asialofetuin (100 mg/kg) reduced hepatic radioactivity to 3.54%. Gel chromatography indicates arabinogalactan is a single species of 19 kDa, while light scattering gave a molecular weight of 40 kDa. Glycosyl linkage analysis of arabinogalactan is consistent with a highly branched structure comprising a backbone of 1,3-linked galactopyranose connected by 1,3-glycosidic linkages, comprised of 3,4,6-,3,6-, and 3,4- as well as 3-linked residues. In the carbon-13 NMR spectra, the major resonances of arabinogalactan are assigned to beta-galactopyranose, beta-arabinofuranose, and beta-arabinopyranose. Arabinogalactan produced no adverse reactions in single intravenous dose (mouse, 5000 mg/kg) and repeat dose toxicity studies (rats, 500 mg/kg/day, 90 days). When tritiated arabinogalactan was injected, radioactivity cleared from the liver with a half-life of 3.42 days. Arabinogalactan has properties that make it suitable as a carrier for delivering diagnostic or therapeutic agents to hepatocytes via the asialoglycoprotein receptor.

Early postnatal estrogen organizes sex differences in the extinction of a CRF running response.

In the present study the organizational effects of sex steroids on the sexually dimorphic extinction of a continuously food-rewarded running response were investigated. Gonadally intact female rats neonatally treated from day 1 to day 8 of the postnatal life with estradiol benzoate (EB), dihydrotestosterone (DHT) or vehicle, and males treated in the same period with the antiandrogen ciproterone acetate (AC), the estrogen antagonist tamoxifen (TX) or vehicle were studied in adulthood during the acquisition and extinction phases of the response in a short and narrow runway. No difference in performance between groups was obtained in the response acquisition. However, during extinction control males extinguished faster than control females. DHT treatment to females and neonatal CA administration to males had no effect on the expression of sexual dimorphism. Conversely, TX administration to the males increased male's resistance to extinction at the levels shown by control or DHT females, whereas the females treated with EB exhibited similar extinction rates to those observed in nonhormonal treated or CA males. This finding suggests that the organizational effect of testosterone on the sexually dimorphic behavior studied in the present report are mediated by testosterone conversion to estradiol throughout the aromatization pathway in the brain.

Regulation of neutrophil superoxide by antichymotrypsin-chymotrypsin complexes.

The ability of neutrophils to generate free radicals is a crucial component of host defense (Babior, B. M. (1978) N. Engl. J. Med. 298, 659-668, 721-725. Neutrophil oxidants, however, can cause significant host tissue destruction (Weiss, S. J. (1989) N. Engl. J. Med. 320, 365-376), and the regulation of free radical production is not well understood. We have previously shown that recombinant antichymotrypsin (rACT), a serine protease inhibitor, inhibits superoxide production in intact neutrophils (Kilpatrick, L., Johnson, J. L., Nickbarg, E. B., Wang, Z., Clifford, T. F., Banach, M., Cooperman, B. S., Douglas, S. D., and Rubin, H. (1991) J. Immunol. 146, 2388-2393). Using a cell-free NADPH oxidase preparation, we now demonstrate that rACT alone has no effect on superoxide production and that antichymotrypsin-chymotrypsin (rACT.CT) complexes are required to inhibit superoxide, suggesting that neutrophil chymotrypsin-like proteases produce conformational changes in ACT, allowing it to become active in regulating superoxide production. Additionally, we have identified NADPH oxidase itself as the target for rACT.CT and have demonstrated that rACT.CT interferes specifically with activation of the NADPH oxidase without changing the Km for NADPH or the rate constant describing the rate-limiting step in activation. These observations suggest an important role for antichymotrypsin in the regulation of NADPH-oxidase activation, which is a prerequisite for neutrophil superoxide production, and predict possible therapeutic uses for rACT in conditions where unregulated neutrophil-free radical production has been implicated in the mechanism of tissue destruction.

Effects of early postnatal gonadal steroids on extinction of a continuously food-rewarded running response.

In the present work the existence of sex differences (Experiment 1) on the acquisition and extinction of a continuously reinforced response in a short and narrow runway (100 x 9 x 10 cm) were investigated. In addition to the investigation of the basic sex differences in Experiment 1, the effect of postpuberal gonadectomy of male and female rats and the role of the early postnatal gonadal steroids on these situations were also examined in Experiments 2 and 3, respectively. In all experiments, no sex differences were found in acquisition. However, males extinguished faster than female rats. Gonadectomy of both sexes in adulthood, although it increases their latencies in acquisition, did not affect the differences between sexes during extinction. In contrast, in Experiment 3 female androgenization and male orchidectomy on day one after birth reversed the direction of sex differences found between control rats in the extinction period. Our findings suggests that the observed sex differences in extinction may be due to an underlying sexual dimorphism in the response inhibition process.