Características clínicas, manejo y riesgo de complicaciones a un año en pacientes con insuficiencia cardíaca con y sin diabetes tipo 2 en España / Clinical characteristics, management, and one-year risk of complications among patients with heart failure with and without type 2 diabetes in Spain

Objetivos: Describir las características clínicas y el manejo terapéutico y determinar los eventos cardiovasculares tras un año de seguimiento en una población contemporánea con insuficiencia cardíaca (IC) con y sin diabetes tipo 2 en España. También se analizó en la población DAPA-HF (pacientes que cumplieron la mayoría de los criterios de inclusión del estudio DAPA-HF) y en los pacientes tratados basalmente con inhibidores SGLT2.Métodos: Estudio observacional, retrospectivo, poblacional, empleando la base de datos BIG-PAC. La fecha índice fue 1 de enero de 2019. Se seleccionaron sujetos≥18 años que recibieron tratamiento por IC en 2019. Se analizaron los eventos durante 2019.Resultados: Se identificaron 21.851 pacientes con IC (78±11,3 años; 53% varones; 50,9% IC con fracción de eyección reducida; 44,5% en clase funcional NYHA II). La prevalencia de IC fue del 1,88% y la incidencia 2,83 por 1.000 pacientes-año. El 66,1% tomaba inhibidores del sistema renina-angiotensina, el 69,4% betabloqueantes, el 31,2% antialdosterónicos y el 7,5% sacubitrilo/valsartán. Durante el año de seguimiento, el 29,8% fue hospitalizado por descompensación de la IC (tiempo medio primer evento 120,9±72,5 días), un 12,3% murieron, un 8,1% murieron durante la hospitalización. Los eventos fueron más frecuentes en los pacientes con diabetes tipo 2. Las hospitalizaciones por IC fueron más comunes en la población similar a DAPA-HF.Conclusiones: En España, la población con IC es anciana y tiene muchas comorbilidades. Aproximadamente la mitad de los pacientes tienen IC con fracción de eyección reducida. Existe margen de mejora en el manejo de la IC, en particular mediante el empleo de aquellos fármacos que reducen tanto la hospitalización por IC como la mortalidad, para disminuir la carga de IC (AU)

Objective: This work aims to describe the clinical characteristics and therapeutic management and to determine cardiovascular outcomes after one year of follow-up in a contemporaneous population with heart failure (HF) with and without type 2 diabetes in Spain. These factors were also analyzed in the DAPA-HF-like population (patients who met most inclusion criteria of the DAPA-HF trial) and in patients treated with SGLT2 inhibitors at baseline.Methods: This work is an observational, retrospective, population-based study using the BIG-PAC database. The index date was January 1, 2019. People aged≥18 years who received care for HF in 2019 were selected. Events that occurred in 2019 were analyzed.Results: We identified 21,851 patients with HF (age 78.0±11.3 years, 53.0% men, 50.9% with HF with reduced left ventricular ejection fraction, 44.5% in NYHA functional class II). HF prevalence was 1.88% and incidence was 2.83 per 1,000 person-years. Regarding HF treatments, 66.1% were taking renin-angiotensin system inhibitors, 69.4% beta blockers, 31.2% aldosterone antagonists, and 7.5% sacubitril/valsartan. During the year of follow-up, 29.8% had HF decompensation which led to hospitalization (mean time to first event of 120.9±72.5 days), 12.3% died, and 8.1% died during hospitalization. Events were more common among patients with type 2 diabetes. Hospitalizations for HF were more common in the DAPA-HF-like population.Conclusions: In Spain, the population with HF is elderly and has many comorbidities. Approximately half of patients have HF with reduced left ventricular ejection fraction. There is room for improvement in HF management, particularly through the use of drugs that reduce both HF hospitalization and mortality, in order to reduce the burden of HF (AU)

The impact of our fight.

The association of parents of children and adolescents with cancer (APNACC), is a nongovernmental organization law institution, with legal status, nonprofit and social aid, whose mission, vision and objectives is to ensure the rights of the children and adolescents so that they are not violated, in addition to guiding and directing parents who enter this world of childhood and adolescent cancer, because we believe that addressing in time saves lives and optimizes resources. Through this article, it is intended to describe the impact that APNACC has had on this cause, the fight against childhood and adolescent cancer; from achieving a state law for free care for catastrophic and orphan or rare diseases, to obtaining approval of a basic list of medications.

Clinical characteristics, management, and one-year risk of complications among patients with heart failure with and without type 2 diabetes in Spain.

OBJECTIVE: This work aims to describe the clinical characteristics and therapeutic management and to determine cardiovascular outcomes after one year of follow-up in a contemporaneous population with heart failure (HF) with and without type 2 diabetes in Spain. These factors were also analyzed in the DAPA-HF-like population (patients who met most inclusion criteria of the DAPA-HF trial) and in patients treated with SGLT2 inhibitors at baseline. METHODS: This work is an observational, retrospective, population-based study using the BIG-PAC database. The index date was January 1, 2019. People aged ≥ 18 years who received care for HF in 2019 were selected. Events that occurred in 2019 were analyzed. RESULTS: We identified 21,851 patients with HF (age 78.0 ± 11.3 years, 53.0% men, 50.9% with HF with reduced left ventricular ejection fraction, 44.5% in NYHA functional class II). HF prevalence was 1.88% and incidence was 2.83 per 1,000 person-years. Regarding HF treatments, 66.1% were taking renin-angiotensin system inhibitors, 69.4% beta blockers, 31.2% aldosterone antagonists, and 7.5% sacubitril/valsartan. During the year of follow-up, 29.8% had HF decompensation which led to hospitalization (mean time to first event of 120.9 ± 72.5 days), 12.3% died, and 8.1% died during hospitalization. Events were more common among patients with type 2 diabetes. Hospitalizations for HF were more common in the DAPA-HF-like population. CONCLUSIONS: In Spain, the population with HF is elderly and has many comorbidities. Approximately half of patients have HF with reduced left ventricular ejection fraction. There is room for improvement in HF management, particularly through the use of drugs that reduce both HF hospitalization and mortality, in order to reduce the burden of HF.

Factors that influence magnetic orientation in Caenorhabditis elegans.

Magnetoreceptive animals orient to the earth's magnetic field at angles that change depending on temporal, spatial, and environmental factors such as season, climate, and position within the geomagnetic field. How magnetic migratory preference changes in response to internal or external stimuli is not understood. We previously found that Caenorhabditis elegans orients to magnetic fields favoring migrations in one of two opposite directions. Here we present new data from our labs together with replication by an independent lab to test how temporal, spatial, and environmental factors influence the unique spatiotemporal trajectory that worms make during magnetotaxis. We found that worms gradually change their average preferred angle of orientation by ~ 180° to the magnetic field during the course of a 90-min assay. Moreover, we found that the wild-type N2 strain prefers to orient towards the left side of a north-facing up, disc-shaped magnet. Lastly, similar to some other behaviors in C. elegans, we found that magnetic orientation may be more robust in dry conditions (< 50% RH). Our findings help explain why C. elegans accumulates with distinct patterns during different periods and in differently shaped magnetic fields. These results provide a tractable system to investigate the behavioral genetic basis of state-dependent magnetic orientation.

Infrecuente complicación de páncreas ectópico: obstrucción intestinal por pseudoquiste pancreático en píloro / Infrequent complication of heterotopic pancreas: intestinal obstruction by pancreatic pseudocyst in pylorus

Resumen: Presentamos un caso un hombre de 53 años con antecedentes de reflujo gastroesofágico y pirosis con varias visitas al servicio de urgencias por vómitos, con antecedentes de consumo crónico de alcohol. La TC sin y con contraste endovenoso mostró a nivel del píloro una lesion ovoidea de paredes gruesas con captación similar al tejido pancreático, con un gran componente quístico bien delimitado que condiciona una obstrucción intestinal. La ecografía confirma la presencia de una lesión quística con ecos móviles en su interior. Tras la realización de antrectomía, el estudio histológico revela un pseudoquiste pancreático sobre páncreas ectópico, siendo esta presentación muy infrecuente, con pocos casos descritos hasta la fecha. Conclusión: Los hallazgos clínico-radiológicos con TC y US de páncreas ectópico pueden orientar el diagnóstico, aunque no son concluyentes. El diagnóstico definitivo se realiza mediante estudio histológico.

Abstract: A 53 year-old male with a past history of chronic alcohol intake, presents with an intestinal obstruction. A CT scan shows an ovoid tumor in pylorus with a great cystic component, thick wall and delimited rim, causing gastric retention. Its walls have similar enhancing pattern as the pancreatic tissue. Ultrasound revealed the presence of a cystic tumor with mobile echoes inside. After antrectomy the histological study reports pancreatic pseudocyst hosted in ectopic pancreas. This is an unusual presentation and only a few cases have been reported. Conclusion: The clinical and radiographic findings of ectopic pancreas are non-specific. Definitive diagnostic requires histological study.

A case of massive hemoptysis related to a smoking-history: an acquired form of the Dieulafoy's disease?

The hypervascularization of the bronquial wall, secondary to chronic bronchopulmonary inflammation is a bleeding etiology in smokers, but insufficient to explain certain massive recurrent cases. We report a case of a woman with a smoking history who presented a recurrent and massive hemoptysis. A diagnostic study with laboratory tests, bronchoscopy, computed tomography and echocardiogram did not identify the etiological cause. However, bronchial arteriography showed right and left bronchial tortuous and dilated arteries and demonstrated that a bronchovascular fistula was the origin of the hemoptysis. An acquired form of the Dieulafoy's disease in this context of a smoking history might justify such findings. Bronchial arteriography as a diagnostic method should be the preferred choice rather than bronchoscopy in these cases.

Mecanobiología de los huesos maxilares. I. Conceptos generales / Mechanobiology of maxillary bones. I. Geneal concepts

La mecanobiología ósea se encarga de la interacción entre las señales mecánicas y los mecanismos moleculares en las células y el tejido óseo. El estudio actual de esta disciplina engloba los modelos informáticos, la biología molecular y las técnicas de imagen en alta resolución. En este artículo se revisan los conceptos generales que se estudian en la mecanobiología y biomecánica de los hueso maxilares. Se establecen las principales propiedades biomecánicas del hueso en las diferentes escalas de medición y determinados factores que influyen en la reacción del hueso perimplantario ante las cargas biomecánicas (AU)

Bone mechanobiology deals with connection between mechanical signals and molecular events in cells and bone tissue. The current study on this subject involves computer models, molecular biology and high resolution imaging of bone. This paper reviews general concepts which take place on mechanobiology and biomechanics of maxillary bones. Mechanical features in several dimensional levels are studied and some factors with influence on perimplantary bone are also evaluated (AU)

Perspectivas actuales del duelo en el fallecimiento de un reciÚn nacido / Perspectives in the grief of a newborn child death

La muerte constituye un evento cotidiano en la medicina, sin embargo, los eventos psicológicos que la acompañan y el enfrentamiento humano de ella ha sido estudiado pocas veces con rigurosidad cientifica. Hace 25 años, frente a la muerte de un reciÚn nacido, se recomendaba que la madre no tuviese contacto con el niño, administrar tranquilizantes a la familia para evitar toda manifestación emocional, no hablar del tema, olvidar al niño y tener otros hijos. Las recomendaciones actuales son diametralmente opuestas, pero aunque hay mes información objetiva, a veces sistemáticamente obtenida, aún son escasos los estudios bien controlados. En general muchas guias clinicas se fundamentan en reportes cualitativos del duelo de unos pocos padres y opiniones de especialistas como psiquiatras o psicoterapeutas. El propósito de este articulo, basado en la literatura y en la experiencia clínica de los autores, es sugerir a partir del conocimiento actual, pautas que faciliten el proceso de acompañamiento de los padres en el fallecimiento de un reciÚn nacido.

Active heterotrophic and autotrophic biomass distribution between fixed and suspended systems in a hybrid biological reactor.

This paper presents the results obtained when modifying sludge retention time (SRT 8, 5, and 3.7 days during phases A, B and C respectively) for a hybrid biological reactor (HR) compared with a classical activated sludge process. The study was conducted by following active biomass evolution and distribution for two lab-scale pilots plants operating with the same conditions, one acting as HR and the other as the control reactor (CR) without support material. At the end of phase C, support material was split into two fractions between both reactors to study the effect of support to reactor volume ratio (Fr). Active biomasses in suspended and fixed systems were calculated using respirometric techniques. Evolutions of active autotrophic and heterotrophic biomasses for both reactors are presented during all the operational periods and it is observed that in the HR biomass concentrations are up to double that in the CR, mainly due to the presence of support material. When studying biomass distribution in HR, autotrophic biomass is mainly located over the support material (from 95% to 99% during periods A and C respectively) while only about 60% of heterotrophic biomass is located over the support.

Estudio descripiivo de los aspectos emocionales asociados a la infertilidad y su tratamiento

El objetivo de este estudio fue describir los principales aspectos emocionales asociados a la infertilidad y su tratamiento. Con este fin, se evaluaron 106 pacientes infértiles, 72 mujeres y 34 varones, en tratamiento en Unidades de Medicina Reproductiva de la ciudad de Santiago. Se encontraron diferencias en la reacción psicológica de mujeres y hombres. Mientras en las primeras predominó la inestabilidad del ánimo (75%), pena (68,1%) y rabia (50%), entre los varones fueron más frecuentes la ansiedad (46,7%), la pena (36,7%) y la inestabilidad del ánimo (33,3%). En lo laboral, las mujeres expresaron dificultades para asistir a los controles y la percepción de menoscabo en el rendimiento. Los varones a menudo manifestaron tener que trabajar más para asumir los gastos. En ambos sexos se observó una asociación entre acumulación de vivencias negativas y mayores grados de compromiso en los ámbitos social y laboral. También ambos sexos coincidieron en opinar que la infertilidad afecta más la vida sexual (33,7%) que la relación de pareja (15,4%).

The aim of this study was to describe the main emotional aspects associated to infertility and its treatment. One hundred and six infertile patients (72 women, 34 men) undergoing treatment in Reproductive Medicine Units of the city of Santiago were assessed. Differences in the psychological reactions of women and men were found. Mood instability (75%), sorrow (68.1%) and anger prevailed among women, whereas anxiety (46.7%), sorrow (36.7%) and mood instability (33.3%) were the most common emotions reported by men. In terms of work, women expressed difficulties to attend medical appointments and deterioration of job performance. Men frequently undertook additional work load in order to pay treatment expenses. An association between negative emotional experiences and greater social and work impairment was found. Both sexes coincided in that infertility disturbs sexual life (33.7%) to a greater degree than marital relationship (15.4%).

Percepcion del aaciente infertil acerca del equipo medico tratante

El objetivo de este estudio fue describir la percepción del paciente infértil acerca del equipo médico tratante y conocer sus expectativas de recibir apoyo emocional. Se evaluaron 106 pacientes infértiles, 72 mujeres y 34 varones, en tratamiento en Unidades de Medicina Reproductiva de la ciudad de Santiago. Los pacientes evaluaron como buena la información entregada por el médico. No obstante, la mayoría (89%) declaró desear recibir más información sobre infertilidad. La acogida por parte del equipo médico tratante fue evaluada como regular (promedio 3,9 en escala 1 a 5), influyendo negativamente en la percepción de los pacientes la dificultad en el contacto telefónico y la falta de continuidad del equipo tratante. En otros aspectos la percepción de acogida fue positiva, tanto en el contexto del hospital universitario como en el de las clínicas privadas. Para las mujeres, haber sido citadas con su pareja se correlacionó positivamente con la percepción de ser escuchadas por su médico.

The aim of this study was to describe the perception of the infertile patient about the medical team and to determine his (her) expectations about receiving emotional support. One hundred and six infertile patients (72 women, 34 men) undergoing treatment in Reproductive Medicine Units of the city of Santiago were assessed. Patients reported that information given by their physicians was good. Nevertheless, most of them said they would like to receive more information on infertility. Receptivity of the medical team was rated as moderate. Difficulties in contacting the medical team by phone and lack of continuity of the medical staff negatively influenced patient's perception about the receptivity of the medical team. Regarding to other aspects, patients tended to view favourably the receptivity of the medical team, both in university hospitals and private clinics. For Women, having been asked to attend appointments with their partners positively correlated with the perception of being heard by their physicians.

Comparison of the efficacy and tolerability of fluvastatin extended-release and immediate-release formulations in the treatment of primary hypercholesterolemia: a randomized trial.

BACKGROUND: A new extended-release (ER) formulation of fluvastatin 80 mg has been developed for once-daily treatment of primary hypercholesterolemia. OBJECTIVE: The purpose of this study was to compare the lipid-lowering efficacy and tolerability of fluvastatin ER (80 mg once daily) versus fluvastatin immediate-release (IR) (40 mg once or twice daily). METHODS: Following a 4-week placebo/dietary run-in period, patients with primary hypercholesterolemia type IIa or IIb (low-density lipoprotein cholesterol ILDL-C] > or = 160 mg/dL and triglycerides [TG] < or = 400 mg/dL) were randomized (2:1:1) to receive fluvastatin ER 80 mg once daily at bedtime (QPM), fluvastatin IR 40 mg QPM, or fluvastatin IR 40 mg BID for 24 weeks. Patients who had homozygous familial hypercholesterolemia; type I, III, IV, V, or secondary hyperlipoproteinemia; diabetes; or evidence of liver or renal impairment were excluded. At weeks 0, 2, 4, 8, 12, 16, 20, and 24 of the active-treatment period, levels of LDL-C, high-density lipoprotein cholesterol (HDL-C), TG, and total cholesterol (TC) were measured. RESULTS: Of the 1183 patients enrolled, 695 were randomly assigned to treatment--346 to fluvastatin ER 80 mg QPM, 174 to fluvastatin IR 40 mg QPM, and 175 to fluvastatin IR 40 mg BID. Patients were well matched between groups, with a mean age of approximately 56 years and body mass index of 27 kg/m2; 56.0% of patients (389/695) were female and 97.7% (679/695) were white. Fluvastatin ER 80 mg QPM lowered LDL-C levels significantly more than did fluvastatin IR 40 mg QPM (33.7% vs 24.4%; P < 0.001) and as effectively as fluvastatin IR 40 mg BID (33.9%). More than half of the patients administered fluvastatin ER 80 mg QPM and IR 40 mg BID achieved reductions in LDL-C levels of > or = 35%; more than half of those administered fluvastatin IR 40 mg QPM experienced reductions in LDL-C levels of > or = 25%. The mean reductions in LDL:HDL ratio, TC, and apolipoprotein B levels in the fluvastatin ER 80 mg QPM group were significantly greater than the reductions in the IR 40 mg QPM group (P < 0.001). In patients with mixed dyslipidemia, fluvastatin ER 80 mg reduced triglycerides by 21.8% (median 28%) and increased HDL-C by 14.5%. Fluvastatin ER 80 mg QPM was well tolerated, with incidences of clinically notable elevations in alanine aminotransferase, aspartate aminotransferase, and creatine kinase levels and musculoskeletal adverse events comparable to those in the IR 40 mg QPM group. CONCLUSION: The ER 80-mg formulation of fluvastatin is effective and well tolerated as a once-daily starting and maintenance treatment for primary hypercholesterolemia.

Endothelin ET(B) receptors counteract venoconstrictor effects of endothelin-1 in anesthetized rats.

The inhibitory effects of BQ 788 (3 mg/kg, i.v., ET(B)-receptor antagonist) on endothelin-1 (ET-1)- or IRL 1620 (ET(B)-receptor agonist)-induced changes in mean arterial pressure (MAP), mean circulatory filling pressure (MCFP, driving force of venous return), arterial resistance (RA), venous resistance (RV) and cardiac output (CO) were characterized in 6 groups of pentobarbital-anesthetized rats. ET-1 or IRL 1620 (0.5, 1 and 2 nmol/kg, i.v.) dose-dependently increased MAP, RA, RV and MCFP and decreased CO. Maximum changes in RA, RV and CO elicited by ET-1 were greater than those by IRL 1620. Equimolar doses of ET-1 and IRL 1620 also caused similar initial transient decreases in MAP. BQ 788 alone slightly elevated MCFP, but did not alter other variables. The ET(B)-blocker abolished all changes elicited by IRL 1620, but only partially inhibited its responses on MCFP, showing the presence of BQ 788-insensitive receptors. BQ 788 also abolished ET-1's depressor response, partially inhibited its effect on MCFP, and markedly augmented its effects on RA, RV and CO. Thus, ET(B)-receptors counteract the sustained constrictor effects of ET-1 on arterial and venous resistance vessels Our results indicate a substantial arterial and venous dilator role for ET(B) receptors.

Protective effects of ethynylestradiol on the hemodynamic changes induced by lipopolysaccharide in anesthetized rats.

Estrogen pretreatment has been reported to protect rats from death induced by endotoxin. We investigated the effects of posttreatment with a synthetic estrogen, ethynylestradiol, on arterial pressure and hemodynamics in thiobutabarbitone-anesthetized rats challenged with Escherichia coli lipopolysaccharide. Rats were i.v. injected with lipopolysaccharide (1 mg/kg) followed by vehicle or a single dose of ethynylestradiol (0.25, 0.5, or 1 mg/kg) 1 h later. Another group (time-matched control) was given the vehicle. In the time-control group, there was a slight decrease in mean arterial pressure (-10 +/- 3 mm Hg) but no significant changes in cardiac output, total peripheral resistance, or heart rate over the 6-h study period. Lipopolysaccharide progressively reduced mean arterial pressure and cardiac output (-27 +/- 8 mm Hg and -52 +/- 6 ml/min, after 6 h) and increased total peripheral resistance and heart rate (+0.33 +/- 0.10 mm Hg/min/ml and +21 +/- 13 beats/min, after 6 h). None of the time-control rats died, but 36% of the rats treated with lipopolysaccharide died between 3 and 6 h after endotoxin challenge. Ethynylestradiol, at 0.25 and 0.5 completely, and at 1 mg/kg partially, restored mean arterial pressure and cardiac output at 6 h after injection of lipopolysaccharide. Ethynylestradiol at 0.5 and 1 mg/kg, but not 0.25 mg/kg, completely reversed the increase in total peripheral resistance at 6 h after injection of lipopolysaccharide. Mortality was 14% in each of the three groups of rats given ethynylestradiol 1 h after lipopolysaccharide. Therefore posttreatment with ethynylestradiol attenuated hemodynamic changes in endotoxic shock.

Pharmacology of JB-9315, a new selective histamine H2-receptor antagonist.

1. The histamine H2-receptor antagonistic activity and antisecretory and antiulcer effects of JB-9315 were studied in comparison with the standard H2 blocker ranitidine. 2. In vitro, JB-9315 is a competitive antagonist of histamine H2 receptors in the isolated, spontaneously beating guinea-pig right atrium, with a pA2 value of 7.30 relative to a value of 7.36 for ranitidine. JB-9315 was specific for the histamine H2 receptor because, at high concentration, it did not affect histamine- or acetylcholine-induced contractions in guinea-pig isolated ileum or rat isolated duodenum, respectively. 3. JB-9315 dose dependently inhibited histamine-, pentagastrin- or carbachol-stimulated acid secretion and basal secretion in the perfused stomach preparation of the anesthetized rat. In the pylorus-ligated rat after intraperitoneal administration, total acid output over 4 h was inhibited by JB-9315 with an ID50 of 32.8 mg/kg, confirming its H2-receptor antagonist properties. 4. JB-9315 showed antiulcer activity against cold stress plus indomethacin-induced lesions with an ID50 of 6.8 mg/kg. 5. JB-9315, 50 and 100 mg/kg, inhibited macroscopic gastric hemorrhagic lesions induced by ethanol. In contrast, ranitidine (50 mg/kg) failed to reduce these lesions. 6. These results indicate that JB-9315 is a new antiulcer drug that exerts a cytoprotective effect in addition to its gastric antisecretory activity.

Subtypes of endothelin receptors that mediate venous effects of endothelin-1 in anaesthetized rats.

1. The subtypes of endothelin receptors that mediate the effects of endothelin-1 (ET-1) on mean arterial pressure (MAP), heart rate (HR), mean circulatory filling pressure (MCFP), arterial resistance (RA), cardiac output (CO) and venous resistance (RV) were characterized in 9 groups of pentobarbitone-anaesthetized rats via the injection of ET-1 in the absence and presence of bosentan (Ro 47-0203, ETA- and ETB-receptor antagonist), PD 142893 (ETA- and ETB-receptor antagonist) or FR 139317 (ETA-receptor antagonist), as well as injection of the ETB-receptor agonist, IRL 1620. 2. Cumulative i.v. bolus injections of ET-1 or IRL 1620 (0.5, 1 and 2 nmol kg-1) dose-dependently increased MAP (ET: by 22, 34 and 44; IRL: 8, 17 and 28 mmHg), RA (ET: 62, 108 and 162; IRL: 51, 63 and 86% over baseline), RV (ET: 70, 132 and 179; IRL: 81, 89 and 98% over baseline) and MCFP (ET: 1.1, 1.8 and 1.9; IRL: 0.9, 1.0 and 1.2 mmHg) and reduced CO (ET: -18, -35 and -44; IRL: -24; -26; -25% below baseline). Equimolar doses of ET-1 and IRL 1620 caused similar initial transient depressor responses. Saline did not modify any haemodynamic variables in the time-control group. 3. Bosentan (10 mg kg-1, i.v.) inhibited ET-induced increases in MAP, RV, RA and MCFP and decrease in CO. PD 142893 (22 mg kg-1, i.v.) abolished ET-induced changes on MAP, RV, RA and CO, but did not alter effects on MCFP. Bosentan alone did not cause haemodynamic changes, but PD 142893 alone elevated MCFP (0.9 +/- 0.3 mmHg at 1 h after injection) and did not alter other variables. Both antagonists abolished the initial depressor effects of ET-1. 4. FR 139317 (1 mg kg-1, i.v.) partially inhibited the increases in MAP, RV, RA and MCFP and decreases in CO elicited by ET-1, but did not alter the transient depressor response of ET-1. 5. The results show that both ETA- and ETB-receptors mediate the arterial and venous constrictor effects of ET-1. Bosentan is more efficacious than PD 142893 in inhibiting the venous effects of ET-1.

Effects of endothelin-1 on arterial and venous resistances in anaesthetized rats.

The effects of endothelin-1 and vehicle (0.9% NaCl) on mean arterial pressure, heart rate, mean circulatory filling pressure, systemic arterial resistance, cardiac output and venous resistance were studied in four groups of pentobarbitone-anaesthetized rats, either in presence or absence of phentolamine. I.v. bolus injections of endothelin-1 at 0.5, 1 and 2 nmol/kg dose dependently increased mean arterial pressure (22, 34 and 40 mmHg), arterial resistance (33, 93 and 122% over baseline), venous resistance (40, 117 and 143% over baseline) and mean circulatory filling pressure (1.0, 1.7 and 1.8 mmHg), but decreased heart rate (-16, -21 and -17 beats/min) and cardiac output (-6, -28 and -35% below baseline). The vehicle did not significantly alter any of these variables. During the continuous infusion of phentolamine (300 microg/kg per min), endothelin-1 caused similar increases in arterial resistance, venous resistance and mean circulatory filling pressure, similar reduction in cardiac output but significantly greater pressor and bradycardic responses, suggesting that the arterial and venous constrictor effects of endothelin-1 are not due to sympathetic activation and the stimulation of alpha-adrenoceptors. The results show that endothelin-1 raised mean arterial pressure via the increment in systemic arterial resistance, since cardiac output was markedly reduced. This decrease in cardiac output was mediated by increases in arterial as well as venous resistances. The vasoconstrictor and venoconstrictor effects of endothelin-1 were independent of sympathetic tone.

Reversal of in vitro lipopolysaccharide-induced suppression of contraction in rat aorta by NG-nitro-arginine, diphenyleneiodonium and di-2-thienyliodonium.

The effects of NG-nitro-L-arginine (L-NNA), D-NNA, diphenyleneiodonium and di-2-thienyliodonium on contraction were studied in endothelium-denuded rat aortic rings incubated for 4 h with lipopolysaccharide (10 mu g ml-1) or vehicle. Lipopolysaccharide reduced Emax and increased EC50 of the phenylephrine (10-9-10-5 M) curve. Addition of D-NNA (4, 6 x 10-4 M), L-NNA (1, 10 x 10-6 M) and diphenyleneiodonium (1, 3 x 10-7 M), but not di-2-thienyliodonium (10-7 M), increased Emax and reduced EC50 of the phenylephrine curve of lipopolysaccharide-incubated but not control rings. Therefore, D-NNA, L-NNA and diphenyleneiodonium, but not di-2-thienyliodonium, inhibit inducible NO synthase in vascular smooth muscles.

JB-9322, a new selective histamine H2-receptor antagonist with potent gastric mucosal protective properties.

1. JB-9322 is a selective histamine H2-receptor antagonist with gastric antisecretory activity and mucosal protective properties. 2. The affinity of JB-9322 for the guinea-pig atria histamine H2-receptor was approximately 2 times greater than that of ranitidine. 3. In vivo, the ID50 value for the inhibition of gastric acid secretion in pylorus-ligated rats was 5.28 mg kg-1 intraperitoneally. JB-9322 also dose-dependently inhibited gastric juice volume and pepsin secretion. In gastric lumen-perfused rats, intravenous injection of JB-9322 dose-dependently reduced histamine-, pentagastrin- and carbachol-stimulated gastric acid secretion. 4. JB-9322 showed antiulcer activity against aspirin and indomethacin-induced gastric lesions and was more potent than ranitidine. 5. JB-9322 effectively inhibited macroscopic gastric haemorrhagic lesions induced by ethanol. Intraperitoneal injection was effective in preventing the lesions as well as oral treatment. The oral ID50 value for these lesions was 1.33 mg kg-1. By contrast, ranitidine (50 mg kg-1) failed to reduce these lesions. In addition, the protective effect of JB-9322 was independent of prostaglandin synthesis. 6. These results indicate that JB-9322 is a new antiulcer drug that exerts a potent cytoprotective effect in addition to its gastric antisecretory activity.