Cigarette smoke induces pulmonary arterial dysfunction through an imbalance in the redox status of the soluble guanylyl cyclase.

Chronic obstructive pulmonary disease (COPD), whose main risk factor is cigarette smoking (CS), is one of the most common diseases globally. Some COPD patients also develop pulmonary hypertension (PH), a severe complication that leads to premature death. Evidence suggests reactive oxygen species (ROS) involvement in COPD and PH, especially regarding pulmonary artery smooth muscle cells (PASMC) dysfunction. However, the effects of CS-driven oxidative stress on the pulmonary vasculature are not completely understood. Herein we provide evidence on the effects of CS extract (CSE) exposure on PASMC regarding ROS production, antioxidant response and its consequences on vascular tone dysregulation. Our results indicate that CSE exposure promotes mitochondrial fission, mitochondrial membrane depolarization and increased mitochondrial superoxide levels. However, this superoxide increase did not parallel a counterbalancing antioxidant response in human pulmonary artery (PA) cells. Interestingly, the mitochondrial superoxide scavenger mitoTEMPO reduced mitochondrial fission and membrane potential depolarization caused by CSE. As we have previously shown, CSE reduces PA vasoconstriction and vasodilation. In this respect, mitoTEMPO prevented the impaired nitric oxide-mediated vasodilation, while vasoconstriction remained reduced. Finally, we observed a CSE-driven downregulation of the Cyb5R3 enzyme, which prevents soluble guanylyl cyclase oxidation in PASMC. This might explain the CSE-mediated decrease in PA vasodilation. These results provide evidence that there might be a connection between mitochondrial ROS and altered vasodilation responses in PH secondary to COPD, and strongly support the potential of antioxidant strategies specifically targeting mitochondria as a new therapy for these diseases.

Tissue-specific up-regulation of arginase I and II induced by p38 MAPK mediates endothelial dysfunction in type 1 diabetes mellitus.

BACKGROUND AND PURPOSE: Emerging evidence suggests a selective up-regulation of arginase I in diabetes causing coronary artery disease; however, the mechanisms behind this up-regulation are still unknown. Activated p38 MAPK has been reported to increase arginase II in various cardiovascular diseases. We therefore tested the role of p38 MAPK in the regulation of arginase I and II expression and its effect on endothelial dysfunction in diabetes mellitus. EXPERIMENTAL APPROACH: Endothelial function was determined in septal coronary (SCA), left anterior descending coronary (LAD) and mesenteric (MA) arteries from healthy and streptozotocin-induced diabetic Wistar rats by wire myographs. Arginase activity and protein levels of arginase I, II, phospho-p38 MAPK and phospho-endothelial NOS (eNOS) (Ser(1177) ) were determined in these arteries from diabetic and healthy rats treated with a p38 MAPK inhibitor in vivo. KEY RESULTS: Diabetic SCA and MA displayed impaired endothelium-dependent relaxation, which was prevented by arginase and p38 MAPK inhibition while LAD relaxation was not affected. Arginase I, phospho-p38 MAPK and eNOS protein expression was increased in diabetic coronary arteries. In diabetic MA, however, increased expression of arginase II and phospho-p38 MAPK, increased arginase activity and decreased expression of eNOS were observed. All these effects were reversed by p38 MAPK inhibition. CONCLUSIONS AND IMPLICATIONS: Diabetes-induced activation of p38 MAPK causes endothelial dysfunction via selective up-regulation of arginase I expression in coronary arteries and arginase II expression in MA. Therefore, regional differences appear to exist in the arginase isoforms contributing to endothelial dysfunction in type 1 diabetes mellitus.

[Emergent drugs (II): the Pharming phenomenon]. / Drogas emergentes (II): el pharming.

The use of medicines, with or without medical prescription, for recreational ends by the young population has received little attention from doctors. In the USA, one in five adolescents has used medicines for recreational purposes, and consultations in Emergency Departments for medicine abuse have exceeded those for illegal drugs. Although few data are available in Spain, such consumption is situated between 3.1 and 8.6% according to surveys. The medicines most used are dextromethorphan and methylphenidate. The former, on sale without prescription, presents a varied symptomatology, dosage and dependent metabolic action, ranging from euphoria to hallucinations. Methylphenidate, taken orally, nasally or intravenously, is used as a stimulant in substitution for cocaine and is one of the medicines most diverted onto the illicit market at the world level. In principle, other substances like modafinil and propofol present a limited incidence of non-medical use, but they have a probable abuse potential that should be borne in mind, above all in the health context. Finally, opiates like fentanyl, oxycodone and buprenorphine, with new pharmaceutical presentations, have recently become generalized in the therapeutic arsenal of many medical specialities; they are giving rise to phenomena of abuse, dependence and diversion towards the illicit market. Demands for detoxification treatment, their mixture with illegal substances, and cases of death should alert us to the abuse of these medicines.

Drogas emergentes (II): el pharming / Emergent drugs (II): the Pharming phenomenon

El uso por la población joven de fármacos con y sin receta médica con fines recreativos, ha tenido escasa atención por los médicos. En USA, uno de cada cinco adolescentes han usado fármacos con finalidad recreativa, y en el servicio de Urgencias, las consultas por abuso de fármacos han superado a las de drogas ilegales. Aunque es España existen pocos datos, este consumo se sitúa, según las encuestas, entre el 3,1 y el 8,6%.Los fármacos más utilizados son el dextrometorfán y el metilfenidato. El primero, de venta sin receta, presenta una sintomatología variable, dosis y acción metabólica dependiente, el cual varía desde la euforia a las alucinaciones. El metilfenidato se utiliza como estimulante sustituto de la cocaína, tanto por vía oral como nasal e intravenosa, siendo uno de los fármacos con más desvío hacia el mercado ilícito a nivel mundial. Otras sustancias como el modafinilo y el propofol presentan un uso no médico en principio de escasa incidencia, pero con un potencial de abuso a tener en cuenta, sobre todo en el ámbito sanitario. Finalmente, opiáceos como el fentanilo, la oxicodona y la buprenorfina, de reciente generalización en el arsenal terapéutico de muchas especialidades médicas y con nuevas presentaciones farmacéuticas, están produciendo fenómenos de abuso, dependencia y comercio ilícito. Las demandas de tratamiento de desintoxicación, la mezcla con sustancias ilegales y los casos de muerte, alertan sobre el abuso de estos fármacos (AU)

The use of medicines, with or without medical prescription, for recreational ends by the young population has received little attention from doctors. In the USA, one in five adolescents has used medicines for recreational purposes, and consultations in Emergency Departments for medicine abuse have exceeded those for illegal drugs. Although few data are available in Spain, such consumption is situated between 3.1 and 8.6% according to surveys. The medicines most used are dextromethorphan and methylphenidate. The former, on sale without prescription, presents a varied symptomatology, dosage and dependent metabolic action, ranging from euphoria to hallucinations. Methylphenidate, taken orally, nasally or intravenously, is used as a stimulant in substitution for cocaine and is one of the medicines most diverted onto the illicit market at the world level. In principle, other substances like modafinil and propofol present a limited incidence of non-medical use, but they have a probable abuse potential that should be borne in mind, above all in the health context. Finally, opiates like fentanyl, oxycodone and buprenorphine, with new pharmaceutical presentations, have recently become generalized in the therapeutic arsenal of many medical specialities; they are giving rise to phenomena of abuse, dependence and diversion towards the illicit market. Demands for detoxification treatment, their mixture with illegal substances, and cases of death should alert us to the abuse of these medicines (AU)

Drogas emergentes (I): las «smart drugs» / Emergent drugs (I): smart drugs

En los últimos años han ganado popularidad unaserie de nuevas drogas, conocidas como smart drugs olegal highs, fácilmente accesibles a través de tiendas online.Ello ocurre sobre todo en los segmentos jóvenesde la población, asociado a su consumo lúdico fundamentalmentedurante los fines de semana.En general son derivados sintéticos de productosnaturales, de los que apenas existe investigación clínicay que no son detectables en los laboratorios de loshospitales.Tres de estos productos, el BZP (1-benzilpiperacina),la mefedrona (4-metilcatinona) y el Spice sonprobablemente los más utilizados en Europa. Los dosprimeros se consumen como alternativas al éxtasis y lacocaína, y se caracterizan por producir un cuadro clínicode tipo simpaticomimético, en ocasiones de consecuenciasgraves, con convulsiones e incluso muerte. ElSpice (mezcla de hierbas con cannabinoides sintéticoscomo el JWH-018, el JWH-073 y el CP 47,497-C8) estáocasionando cuadros de dependencia y esquizofrenia.Aunque las drogas emergentes poseen un aurade seguridad, cada vez hay más experiencia sobre susefectos secundarios(AU)

In recent years, a series of new drugs, known assmart drugs or legal highs, have gaining in popularity.They are easily obtainable through online shops. Thisis happening amongst younger segments of the populationand is associated with recreational consumption,at weekends.In general, they are synthetic derivatives of naturalproducts. There has been hardly any clinical researchinto them and they are not detectable in hospital laboratories.Three of these products, BZP (1-benzylpiperazine),mefedrone (4-methylmethcathinone) and Spice are probablythe most widely used in Europe. The first two areconsumed as an alternative to ecstasy and cocaine andare characterized by their producing a clinical profile ofa sympathetic mimetic type; on occasion, they have seriousconsequences, with convulsions and even death.Spice (a mixture of herbs with synthetic cannabinoidssuch as JWH-018, JWH-073 and CP 47497-C8) is givingrise to profiles of dependence and schizophrenia.Although the emergent drugs have an aura of safety,there is an increasing amount of experience on theirsecondary effects(AU)

Bases del manejo clínico de la intoxicación por humo de incendios «Docohumo Madrid 2010» / Basis for the clinical management of fire smoke poisoning «Docohumo Madrid 2010»

La intoxicación por humo es la principal causa de morbimortalidad en los incendios. El humo es una mezcla de partículas carbonáceas suspendidas en aire caliente y gases tóxicos. De todos ellos, el monóxido carbono (CO) y fundamentalmente el ácido cianhídrico (CNH) son los que van a provocar la anoxia tisular. Las manifestaciones clínicas de la intoxicación por humo son variables. Algunas de las manifestaciones potenciales podrían ser: irritación ocular, dolor de garganta, estridor laríngeo, disfagia, esputo carbonáceo, tos, disnea, laringoespasmo, broncoespasmo, síndrome coronario, coma, hipoxemia, acidosis láctica, cianosis y muerte. En la evaluación de estos enfermos la presencia de hollín en nariz, boca o esputo sugiere intoxicación grave. Niveles de lactato superiores a 10mmol/l indican cifras de cianuro mayores de 40micromol/l. La pulsicooximetría ha supuesto un avance importante para el diagnóstico, valoración y seguimiento de estos pacientes. En el tratamiento será indispensable valorar la necesidad de una intubación temprana. La administración de oxígeno al 100% será esencial. Como antídoto para el cianuro, el de primera elección es la hidroxicobalamina. Su administración ha de ser precoz. Los criterios de administración son: paciente que ha inhalado humo (restos de hollín en boca, faringe o esputo) y que tenga alteraciones neurológicas (confusión, coma, agitación, convulsiones) y además presenta una de las siguiente circunstancias: bradipnea, parada respiratoria, parada cardiorrespiratoria, shock, hipotensión, láctato >8mmol/l o acidosis láctica. Lógicamente el resto del manejo será convencional en función de síntomas o complicaciones (AU)ies

Poisoning by smoke is the main cause of morbidity and mortality in fires. Smoke is a mixture of carbonaceous particles suspended in hot air and toxic gases. Of these, carbon monoxide (CO) and primarily hydrocyanic acid (CNH), are those that provoke tissue anoxia. The clinical manifestations of smoke poisoning are variables. Some of the potential manifestations could be: eye irritation, sore throat, laryngeal stridor, dysphagia, carbonaceous sputum, cough, dyspnea, laryngospasm, bronchospasm, coronary syndrome, coma, hypoxemia, lactic acidosis, cyanosis and death. In the assessment of these patients the presence of soot in the nose, mouth or sputum suggests serious poisoning. Lactate levels higher than 10mmol/L indicates levels of cyanide major than 40micromole/L. The pulse co-oximetry has assumed an important step forward for the diagnosis, appraisal and monitoring of these patients. In the treatment it will be essential to assess the need of an early intubation. The administration of oxygen to the 100% will be essential. As an antidote to the cyanide, the first-choice is the hydroxocobalamin. Its administration has to be early. Its administration criteria are: patient who has inhaled smoke (remnants of soot in the mouth, pharynx or sputum) and has neurological disorder (confusion, coma, agitation, seizures) and also presents one of the following circumstances: bradypnea, respiratory arrest, cardiorespiratory arrest, shock, hypotension, lactate >8mmol/L or lactic acidosis. Logically, the rest of the management will be conventional depending on symptoms or complications (AU)

[Basis for the clinical management of fire smoke poisoning "Docohumo Madrid 2010"]. / Bases del manejo clínico de la intoxicación por humo de incendios «Docohumo Madrid 2010¼

Poisoning by smoke is the main cause of morbidity and mortality in fires. Smoke is a mixture of carbonaceous particles suspended in hot air and toxic gases. Of these, carbon monoxide (CO) and primarily hydrocyanic acid (CNH), are those that provoke tissue anoxia. The clinical manifestations of smoke poisoning are variables. Some of the potential manifestations could be: eye irritation, sore throat, laryngeal stridor, dysphagia, carbonaceous sputum, cough, dyspnea, laryngospasm, bronchospasm, coronary syndrome, coma, hypoxemia, lactic acidosis, cyanosis and death. In the assessment of these patients the presence of soot in the nose, mouth or sputum suggests serious poisoning. Lactate levels higher than 10mmol/L indicates levels of cyanide major than 40micromole/L. The pulse co-oximetry has assumed an important step forward for the diagnosis, appraisal and monitoring of these patients. In the treatment it will be essential to assess the need of an early intubation. The administration of oxygen to the 100% will be essential. As an antidote to the cyanide, the first-choice is the hydroxocobalamin. Its administration has to be early. Its administration criteria are: patient who has inhaled smoke (remnants of soot in the mouth, pharynx or sputum) and has neurological disorder (confusion, coma, agitation, seizures) and also presents one of the following circumstances: bradypnea, respiratory arrest, cardiorespiratory arrest, shock, hypotension, lactate ≥8mmol/L or lactic acidosis. Logically, the rest of the management will be conventional depending on symptoms or complications.

Bases para el manejo clínico de la intoxicación por humo de incendios / Fundamentals in the clinical management of intoxication due to smoke inhalation

La intoxicación por humo es la principal causa de morbimortalidad en los incendios. El humo es una mezcla de partículas carbonáceas suspendidas en aire caliente y gases tóxicos. De todos ellos, el monóxido carbono (CO) y fundamentalmente el ácido cianhídrico(CNH), son los que van a provocar la anoxia tisular. Las manifestaciones clínicas de la intoxicación por humo son variables. Algunas de las manifestaciones potenciales podrían ser: irritación ocular, dolor de garganta, estridor laríngeo, disfagia, esputo carbonáceo, tos, disnea, laringoespasmo, broncoespasmo, síndrome coronario, coma, hipoxemia,acidosis láctica, cianosis y muerte. En la evaluación de estos enfermos la presencia de hollín en nariz, boca o esputo sugiere intoxicación grave. Los valores delactato superiores a 10 mmol/L indican cifras de cianuro mayores de 40 micromol/L. Lapulsicooximetría ha supuesto un avance importante para el diagnóstico, valoración y seguimiento de estos pacientes. En el tratamiento será indispensable valorar la necesidad de una intubación temprana. La administración de oxígeno al 100% será esencial. Como antídoto para el cianuro, el de primera elección es la hidroxicobalamina. Su administración ha de ser precoz. Los criterios de administración son: paciente que ha inhalado humo (restos de hollín en boca, faringe o esputo) y que tenga alteraciones neurológicas (confusión, coma, agitación, convulsiones) y que además presenta una de las siguiente circunstancias: bradipnea, parada respiratoria, parada cardiorrespiratoria, shock, hipotensión, lactato 8 mmol/L o acidosis láctica. Logicamente, el resto del manejo será el convencional en función de síntomas o complicaciones (AU)

Intoxication due to smoke inhalation is the main cause of morbidity and mortality from fires. Smoke is a mixture of carbon particles suspended in hot air containing toxic gases. Carbon monoxide (CO) and cyanuric acid are the gases that are mainly responsible for tissue anoxia. The clinical signs of intoxication due to smoke inhalation vary. They may include eye irritation, sore throat, laryngeal stridor, dysphagia, soot in sputum, cough, breathlessness, laryngeal spasm,bronchospasm, coronary syndrome, coma, hypoxemia, lactic acidosis, cyanosis, and death. A finding of soot in the nostrils, mouth or sputum suggests severe intoxication. Lactate dehydrogenase levels over 10 mmol/L are indicative of cyanuric acid levels over 40 mmol/L. Pulse oximetry has represented an important advance for diagnosis, examination, and follow-up in this setting. The possible need for early intubation must be assessed and oxygen administration (at100%) is essential. The treatment of choice for cyanuric acid poisoning is hydroxocobalamin. This antidote must be administered promptly whenever a patient has inhaled smoke (soot in mouth, throat or sputum), shows neurologic signs(confusion, coma, agitation, convulsions), or has any of the following signs: bradypnea, respiratory arrest, cardiac arrest,shock, hypotension, lactate dehydrogenase over 8 mmol/L, or lactic acidosis. There after, management will be dictated by symptoms or complications (AU)

[Analysis of the poisonings by lithium in a department of internal medicine]. / Análisis de las intoxicaciones por litio ingresadas en un servicio de medicina interna.

INTRODUCTION: Lithium salts have been mainly used in the treatment of bipolar disorder. Because of its narrow therapeutic range, and several well characterised adverse effects, serum lithium levels must be monitored regularly in patients given lithium treatment in order to prevent intoxication. OBJECTIVE: To describe the clinic and toxic characteristics in inpatients at our Clinic Toxicologic Unit. MATERIAL AND METHODS: Descriptive and retrospective study of lithium intoxications in 150 inpatients between 2003 and 2006. Patients were classified based on their neuropsychiathric symptom profile and serum lithium levels. RESULTS: Sixteen of 150 inpatients had lithium intoxication: 58.3% women and 43.8% men; 49.19% +/- 18.49% years old. Lithium was used as treatment of bipolar disorder in 87.5% of cases. The most frequent cause of intoxication was attempted suicide. Using neuropsychiatric parametres, intoxication was moderate in 50% of cases, and mild in 25% and severe or very severe in 25%. Using serum lithium levels, intoxication was very severe in 31.35%, severe in 25%, and slight-moderate in 43.7%. Conservative measures were used as the most frequent treatment (50%), and haemodialfiltration was needed in 37.5%. Mean stay was 4,8 days in acute intoxication, and 11.2 days in chronic. Sequelaes were found in two patients (ataxia). Death was not present. CONCLUSIONS: Lithium intoxications can involve severe complications, even death. Narrow control is encouraged in polymedicated and elderly patients, and in concommitant treatment with antidepressant and neuroleptics.

Análisis de las intoxicaciones por litio ingresadas en un servicio de medicina interna / Analysis of the poisoning by lithium in a department of internal medicine

Introducción: El litio, utilizado principalmente en el tratamiento de los trastornos bipolares, presenta un estrecho margen terapéutico, que junto a sus múltiples interacciones y farmacocinética obliga a una monitorización estrecha de concentraciones plasmáticas para evitar intoxicaciones. Objetivo: Describir características clínicas y toxicológicas de los pacientes ingresados en la Unidad Toxicología Clínica (2003-2006). Material y métodos: Estudio descriptivo y retrospectivo de 16 intoxicaciones por litio, de 150 pacientes ingresados entre los años 2003-2006. Se han utilizado dos escalas: según la clínica y los valores séricos de litio. Resultados: Dieciséis pacientes incluidos (58,3 mujeres y 43,8% hombres, 49,19 ± 18,49 años). Trastorno psiquiátrico más frecuente asociado bipolar (87,5%). Causa más frecuente de intoxicación, intento autolisis (56,3%). Según escala neurológica, 50% intoxicación moderada, 25% leve y grave o muy grave el 25% restante. En relación a los niveles de litemia, 31,35% muy grave, 25% graves, 43.7 % leve-moderado.Tratamiento más utilizado en un 50% conservador, hemodiálisis 37,5%, estancia media 4,8 días en intoxicaciones aguda, y 11,2 días en crónicas. Secuelas sólo en dos pacientes (ataxia), sin ninguna muerte. Conclusiones: Las intoxicaciones por litio conllevan gravedad clínica, complicaciones y graves secuelas, incluso la muerte. Se recomienda vigilancia estrecha en pacientes polimedicados, edad avanzada o en tratamiento concomitante de antidepresivos y neurolépticos

Introduction: Lithium salts have been mainly used in the treatment of bipolar disorder. Because of its narrow therapeutic range, and several well characterised adverse effects, serum lithium levels must be monitored regularly in patients given lithium treatment in order to prevent intoxication. Objetive: To describe the clinic and toxic characteristics in inpatients at our Clinic Toxicologic Unit. Material and methods: Descriptive and retrospective study of lithium intoxications in 150 inpatients between 2003 and 2006. Patients were classified based on their neuropsychiathric symptom profile and serum lithium levels. Results: Sixteen of 150 inpatients had lithium intoxication: 58.3% women and 43.8% men; 49.19% ± 18.49% years old. Lithium was used as treatment of bipolar disorder in 87.5% of cases. The most frequent cause of intoxication was attempted suicide. Using neuropsychiatric parametres, intoxication was moderate in 50% of cases, and mild in 25% and severe or very severe in 25%. Using serum lithium levels, intoxication was very severe in 31.35%, severe in 25%, and slight-moderate in 43.7%. Conservative measures were used as the most frequent treatment (50%), and haemodial filtration was needed in 37.5%. Mean stay was 4,8 days in acute intoxication, and 11.2 days in chronic. Sequelaes were found in two patients (ataxia). Death was not present. Conclusions: Lithium intoxications can involve severe complications, even death. Narrow control is encouraged in polymedicated and elderly patients, and in concommitant treatment with antidepressant and neuroleptics

Alteración local de las partes blandas / Local alterations of the soft tissue

No disponible

[Clinical and ultrastructural evaluation of nasal mucociliary function in HIV-positive patients. Preliminary investigation]. / Evaluación clínica y ultraestructural de la función mucociliar nasal en pacientes VIH+. Investigación preliminar.

Nasal mucociliary transport was studied in 33 HIV-positive patients with different stages of infection. Ciliary ultrastructure was studied in 8 of these cases. At the time of study, 24 patients had respiratory infections. Disturbances in mucociliary transport were found in 25 cases. In 6 of the 8 studies of ciliary ultrastructure, changes in the ciliary axonema were found, particularly in the central and peripheral microtubules.

Mucormycosis of the paranasal sinuses.

Between 1989 and 1992 we had two cases of mucormycosis. The first patient presented with left hemiplegia: radiologic studies showed a right sphenoidal sinus mass, cerebral ischaemic infarction and occlusion of the right carotid artery. The second patient was seen with an abscess of the hard palate after long term steroid therapy. CT scan showed a soft-tissue mass occupying the maxillary sinus, which had eroded its walls and spread to palate, orbit and ethmoidal cells. We have emphasised the presence of hyperglycemia in both cases, the marked tendency of this lesion to invade blood vessels, and the good results obtained by combining liposomal amphotericin B with radical surgical debridement.