Immunohistochemical evidence of melatonin protection on lung tissue during chemotherapy / Evidencia inmunohistoquímica de la protección de la melatonina en el tejido pulmonar durante la quimioterapia

SUMMARY: The present study investigated the possible protective effects of melatonin on Bleomycin, Cisplatin and etoposide (BEP) chemotherapy regimens using immunohistochemistry. Forty male Wistar rats were divided into four groups of ten as; group 1 as untreated control; group 2 as BEP group which received the three cycles of 21 days' regimen each of 0.5¥ dose levels ofBEP (bleomycin 0.75 mg/kg, etoposide 7.5 mg/kg and cisplatin 1.5 mg/kg). Rats in the group 3 (MEL group) received 10 mg/kg/day melatonin once daily. Group 4 received the melatonin (30 min before the BEP injections) and BEP as in groups 2. Proliferating cell nuclear antigen (PCNA) staining was used to detect cell proliferation and caspase-3, caspase-9 and Caspase-8 were detected to investigate apoptosis. PCNA immunostaining in alveolar epithelium, alveolar macrophages and bronchus was weak to moderate in BEP group. However, diffuse and strong caspase immunoreactions for caspase-3, caspase 8- and caspase-9 were detected in the bronchioles epithelium, vascular endothelium, alveolar luminal macrophages in the BEP group. PCNA and caspase immunoreactivities in MEL and Mel + BEP groups were close to the control one. The surface are in the BEP group was significantly reduced as compared to the control one ((P0.05). It can be concluded that BEP regimen can affects negatively on lung tissue and melatonin inhibits lung tissue injuries during BEP chemotherapy.

El presente estudio investigó los posibles efectos protectores de la melatonina en los regímenes de quimioterapia con bleomicina, etopósido y cisplatino (BEP) mediante inmunohistoquímica. Cuarenta ratas Wistar macho se dividieron en cuatro grupos de diez: grupo 1, control sin tratar; grupo 2, quimioterapia con una dosis de 0,5x de BEP (0,75 mg/kg de bleomicina, 7,5 mg/ kg de etopósido y 1,5 mg/kg de cisplatino) con tres ciclos de 21 días cada uno. Las ratas del grupo 3 (grupo MEL) recibieron 10 mg/kg/día de melatonina una vez al día. El grupo 4 (Mel + BEP) recibió melatonina (30 minutos antes de las inyecciones de BEP) y BEP, como en los grupos 2. Se usó la tinción del antígeno nuclear de células en proliferación (PCNA) para detectar la proliferación celular y, caspasa- 3, caspasa-9 y caspasa-8 para investigar apoptosis. La inmunotinción de PCNA en el epitelio alveolar, los macrófagos alveolares y los bronquios varió de débil a moderada en el grupo BEP. Sin embargo, se detectaron inmunorreacciones difusas y fuertes para caspasa-3, caspasa 8- y caspasa-9 en el epitelio de los bronquiolos, endotelio vascular y macrófagos luminales alveolares. Las inmunorreactividades de PCNA y caspasa en los grupos MEL y Mel + BEP fueron similares a las del control. El área de superficie en el grupo BEP se redujo significativamente en comparación con el control (P0,05). Se puede concluir que la quimioterapia con BEP puede afectar negativamente al tejido pulmonar y la melatonina inhibe las lesiones durante la quimioterapia.

Productos intermedios de la cocaína: la pasta base o "paco" / Intermediate products of cocaine: the base paste or "paco"

El uso indebido de drogas se ha convertido en un grave problema a nivel mundial. En los últimos años, en nuestro país se ha incrementado en más del 200% el consumo de pasta base de cocaína (paco). A pesar de que el paco es un producto intermedio en la obtención de cocaína, y que muchos de sus efectos son atribuibles al contenido de esa droga, su consumo produce un cuadro clínico claramente distinto al observado en los consumidores de clorhidrato de cocaína, lo cual puede estar relacionado con su impureza. Sin perjuicio del gran impacto social producido por el consumo de paco, poco se sabe sobre su composición química y menos aún sobre sus efectos crónicos en los distintos órganos ni sobre su fisiopatología. Si bien existe material de autopsia de adictos al paco, los hallazgos están contaminados por la coexistencia en un mismo paciente de múltiples tóxicos. Urge la formación de grupos multidisciplinarios, con moderna tecnología para enfrentar este gravísimo flagelo. (AU)

Drug abuse has become a serious problem worldwide. In recent years, in our country the consumption of cocaine base paste (Paco) has increased by more than 200%. Despite of the fact that Paco is an intermediate product in the manufacture of cocaine, and that many of its effects are attributable to its content, its consumption produces a clearly different clinical picture than that observed in cocaine hydrochloride users, which It may be related to the impurity of this drug. Without prejudice to the great social impact produced by the consumption of this drug, little is known about its chemical composition and even less about its chronic effects on the different organs or its pathophysiology. Although there is an autopsy material for drug addicts, the findings are contaminated by the coexistence of multiple toxins in the same patient. The formation of multidisciplinary groups is urgent, with modern technology to face this very serious scourge. (AU)

Toxicidad pulmonar aguda por amiodarona con dosis baja de impregnación: reporte de caso / Acute amiodarone pulmonary toxicity with low impregnation dose: case report

Se sabe que la amiodarona, un potente antiarrítmico, causa toxicidad pulmonar. La neumonitis intersticial crónica es la presentación más común. Sin embargo, la toxicidad pulmonar aguda es rara y provoca una mayor mortalidad. Se presenta un paciente de 61 años con fibrilación auricular persistente que, tras tratamiento por un mes con amiodarona vía oral a dosis baja de impregnación de 400 miligramos al día, desarrolló toxicidad pulmonar aguda secundaria al antiarrítmico confirmada por radiografía y tomografía. Su caso tuvo resolución después de la suspensión del fármaco y tratamiento con esteroides.

Amiodarone, considered a potent antiarrhythmic, is known to cause pulmonary toxicity. Chronic interstitial pneumonitis is the most common presentation. However, acute pulmonary toxicity is rare and has a higher case fatality rate. We present a 61-year-old patient with persistent atrial fibrillation who, after a one-month treatment with oral amiodarone at a low dose impregnation of 400 mg/day, develops acute pulmonary toxicity, with radiographic and tomographic resolution after antiarrhythmic suspension and steroid treatment.

Mecanismos de los efectos nocivos para la salud de la contaminación atmosférica proveniente de incendios forestales / Mechanisms of noxious effects of wildfire air pollution over human health

Los incendios forestales representan un problema creciente de la salud pública a nivel mundial, especialmente para la población más vulnerable (niños, ancianos, embarazadas y portadores de enfermedades cardiovasculares o respiratorias crónicas) expuesta al humo y a otros contaminantes aéreos. A diferencia de la contaminación atmosférica habitual de grandes urbes, aquella derivada de los incendios forestales tiene una composición diferente y su ocurrencia es esporádica y difícil de prever. La exposición a contaminantes atmosféricos derivados de incendios forestales se asocia a aumento de la morbilidad respiratoria y cardiovascular, mediada por una respuesta inflamatoria pulmonar y sistémica, estrés oxidativo y disfunción endotelial. En sujetos expuestos a humo de incendios forestales se ha observado un aumento en la producción de citoquinas pro-inflamatorias, activación endotelial y disfunción del sistema nervioso autónomo, que produce daño tisular, aumento de los mecanismos protrombóticos, aumento de la presión arterial y cambios en el ritmo cardiaco. Esta revisión analiza los mecanismos que han sido involucrados en generar efectos nocivos para la salud de seres humanos expuestos a material particulado y gases emanados de incendios forestales.

Wildfires represent a growing global public health issue, especially to the most vulnerable segment of the population (children, old people, pregnant women, patients with cardiovascular or respiratory diseases) exposed to smoke and other air borne contaminants generated from these events. In contrast to great cities ' usual atmospheric pollution, that derives from forest fires differ in composition and its occurrence is sporadic and usually unpredictable. Exposure to atmospheric pollutants derived from forest fires has been associated to increased respiratory and cardiovascular morbidity, mediated by an inflammatory systemic response, oxidative stress and endothelial dysfunction. In people exposed to forest fire smoke an increased production of pro-inflammatory cytokines, endothelial activation and autonomic nervous system dysfunction has been observed, that leads to tissue injury, increased prothrombotic response, increased blood pressure and changes in heart rhythm. This review analyzes the mechanisms that have been involved in generating harmful health effects in humans exposed to inhaled particulate matter and gases steaming from wildfires.

Productos de tabaco calentado con especial referencia a IQOS / Heated tobacco products with special reference to IQOS

Los Productos de Tabaco Calentado (PTC) son nuevos dispositivos de consumo de tabaco que se presentan como un producto de reducción del daño. El más difundido es IQOS de Philip Morris. En el aerosol de IQOS se detectan sustancias tóxicas en menor cantidad y concentración que las detectadas en el humo del cigarrillo convencional, a excepción de algunas. Estas sustancias son capaces de producir enfermedad, con alteración de las células del epitelio bronquial y del endotelio vascular y podría producir nuevos daños, como hepato-toxicidad. La cantidad de nicotina de IQOS es muy similar a los cigarrillos convencionales, por lo que es tan adictivo como el cigarrillo normal. La concentración de sustancias tóxicas emitidas al medio ambiente es menor que las del cigarrillo convencional, pero hay riesgo para la salud de los no fumadores expuestos. La mayoría de las personas usan los PTC como complemento a los cigarrillos convencionales, no como alternativa, transformándose en fumadores duales. IQOS puede crear nuevas generaciones adictas a la nicotina, además de renormalizar el consumo de tabaco en la sociedad. Muchas Sociedades Médicas de Enfermedades Respiratorias en el mundo se han manifestado en contra del uso de los PTC, y han propuesto que deben regirse bajo las mismas políticas regulatorias que se aplican a todos los productos de tabaco, en línea con lo establecido por el Convenio Marco de Control del Tabaco de la OMS.

Heated Tobacco Products (HTP) are new tobacco consumption devices that are presented as a harm reduction product. The most widespread is IQOS by Philip Morris. In the IQOS aerosol, toxic substances are detected in a smaller amount and concentration than those detected in conventional cigarettes, with the exception of some of them. These substances are able of inducing disease. They could modify bronchial epithelial cells and vascular endothelium and could cause additional damages, such as hepatotoxicity The amount of nicotine in IQOS is very similar to conventional cigarettes, so it is as addictive as a normal cigarette. The concentration of toxic substances emitted to the environment is lower than those of conventional cigarettes, but there is a health's risk of exposed non-smokers. Most people use HTP as a complement to conventional cigarettes, not as an alternative, becoming dual smokers. IQOS can create new generations addicted to nicotine, in addition to renormalize the tobacco's use in society. Many Medical Societies of Respiratory Diseases around the world have manifested against the use of HTP, and have proposed that they should be subject to the same regulatory policies that applied to all tobacco products, in line with the WHO Framework Convention on Tobacco Control.

Expression dynamics of caveolin-1 in fibroblasts of newborn rats with chronic lung disease and its impact on lung fibroblast proliferation

Abstract Purpose: To evaluate the changes of caveolin-1 in lung fibroblasts in newborn Wistar rats when exposed to hyperoxic conditions, as well as lung fibroblasts cell cycle. Methods: One hundred newborn Wistar rats were randomly divided (50 rats/group) into experimental and control groups, exposed to hyperoxic conditions or normal air, respectively. The fraction of inspired oxygen (FiO2) in the experimental group was 90%, whereas this value was 21% in the control group. Lung fibroblasts were collected on days 3, 7, and 14 of the experiment. Caveolin-1 expression dynamics in lung fibroblasts was assayed in each group by immunofluorescence and Western blot analyses. Flow cytometry (FCM) was used to assess the proportions of lung fibroblasts at different stages of the cell cycle. Results: On day 3, no significant difference in caveolin-1 expression was observed between the hyperoxic and control groups; however, on days 7 and 14, caveolin-1 expression was significantly lower in the hyperoxic group than in the control (P<0.05). No apparent differences were observed in caveolin-1 expression in the control group at the different time points. Using FCM analysis, we showed that the proportion of lung fibroblasts in G0/G1 phase in the hyperoxic group decreased compared to that of the control group on day 7, while the proportion of S-phase cells increased (P<0.05). These differences were more significant when the groups were compared on day 14 (P<0.01). Conclusion: After seven days the exposure to hyperoxic conditions, lung fibroblasts proliferated and caveolin-1 expression decreased.

Progressive Multiple Cystic Changes in Both Lungs in a Patient Treated with Gefitinib for Lung Adenocarcinoma with Multiple Lung Metastases

Gefitinib is regarded as a relatively safe agent for the treatment of an advanced non-small cell lung cancer (NSCLC). Pulmonary toxicity such as interstitial lung disease associated with gefitinib is uncommon with an estimated all time incidence around 1% worldwide. Moreover, a case of gefitinib associated with pulmonary cystic changes has not been reported yet. In this report we present a case of progressive multiple air cystic changes in both lungs in a patient with NSCLC and intrapulmonary metastases who underwent a gefitinib therapy.

El ejercicio físico aumenta el daño pulmonar inducido por la exposición aguda e intermitente a 0, 5 ppm de ozono en ratas juveniles / Physical exercise increases pulmonary damage induced by acute and intermittent exposure to 0.5 ppm of ozone in juvenile rats

El ozono (O3) troposférico es el principal oxidante del esmog fotoquímico. Como es un contaminante aéreo, sus efectos están relacionados con la dosis efectiva = [Concentración] x [tiempo de exposición] x [ventilación minuto]. Objetivo: Determinar si el ejercicio físico -que aumenta la ventilación minuto- puede aumentar el daño pulmonar inducido por la exposición a O3 en ratas en reposo. Material y Métodos: Se usó 4 series de ratas Sprague-Dawley juveniles. Dos series fueron expuestas a 0,5 ppm de O3 (4 h diarias por 2 días) en reposo (n = 13) o durante ejercicio (n = 12). Dos series control respiraron aire filtrado (AF) en reposo (n = 13) o durante sesiones de ejercicio (n = 13), en una rueda vertical giratoria (15 min de ejercicio alternados con 15 min de descanso hasta completar 4 h diarias durante 2 días). Las ratas fueron eutanasiadas y se determinó la razón peso húmedo/peso seco (PH/PS) en el pulmón izquierdo. En el lavado broncoalveolar (LBA) del pulmón derecho, se determinó recuento total de células, proteínas totales y actividad de gamma-glutamiltraspeptidasa (GGT). Resultados: la razón PH/PS y el recuento de células y las proteínas del LBA aumentaron en las ratas en reposo expuestas a O3 comparadas con las ratas en reposo que respiraron AF (p < 0,05 ANOVA & Newman-Keuls). La actividad de GGT en el LBA fue mayor en las ratas que en ejercicio respiraron AF en comparación con las ratas que respiraron AF en reposo (p < 0,05). Hubo aumento de GGT, proteínas y recuento de células en el LBA de la serie [ejercicio + O3] comparada con la serie [reposo + O3] (p < 0,05). Conclusión: El ejercicio físico aumenta el daño pulmonar inducido por la exposición aguda e intermitente a 0,5 ppm de O3 en ratas juveniles.

Tropospheric ozone (O3) is the major oxidant of photochemical smog. Being an air pollutant, its effects are related to effective dose = [Concentration] x [exposure time] x [pulmonary ventilation]. Objective: Determine whether physical exercise -that increases pulmonary ventilation- is able to augment the pulmonary damage induced by O3 exposure in resting rats. Material and Methods: Four series of juvenile Sprague-Dawley rats were used. Two series were exposed to 0.5 ppm O3 (4 hours a day for 2 days) at rest (n=13) or during exercise (n=12). Two control series breathed filtered air (FA) at rest (n=13) or during exercise sessions (n=13), in a vertical rotary wheel (15 min exercise alternated with 15 min resting until to completing 4 hours a day for 2 days). Rats were euthanized and wet weight / dry weight ratio (W/D ratio) was determined in left lung. Total cell counting, total protein content and γ-glutamyltraspeptidase (GGT) activity were determined in the right lung bronchoalveolar lavage fluid (BALF). Results: W/D weight ratio as well as total cell counting and protein content increased in BALF from resting rats exposed to O3 as compared with resting rats breathing FA (p < 0.05 ANOVA & Newman-Keuls test). GGT activity in BALF increased in rats under exercise breathing FA as compared with resting rats breathing FA (p<0.05). GGT, proteins and cells counting increased in BALFfrom series [exercise + O3] as compared to series [resting + O3] (p< 0.05). Conclusion: Physical exercise increases lung damage induced by intermittent and acute 0.5 ppm O3 exposure in juvenile rats.

CD14 C-159T polymorphism and its association with chronic lung diseases: A pilot study on isocyanate exposed population of Central India.

CONTEXT: CD14 functions as a multifunctional receptor for bacterial cell wall components including endotoxin and lipopolysaccharide and is likely to influence the cytokine profile and subsequent immunoglobulin E production in response to antigen/allergen contact in allergic phenotypes. AIMS: The present study was to investigate genetic polymorphism in CD14 gene - 159C/T, which may be one of the risk factor for increased prevalence of Chronic Lung Diseases in the Central India. SETTINGS AND DESIGN: Survivors of Methyl isocyanates toxicity in Bhopal still suffering from various respiratory ailments were examined. MATERIALS AND METHODS: Polymerase chain reaction-restriction fragment length polymorphism was performed to determine the polymorphism of C-159T. RESULTS: The genotype and allelic frequencies were in Hardy-Weinberg’s equilibrium. Prevalence of CC, CT, and TT were 5.5%, 22.2% and 9.25% respectively in asthmatics; 16.6%, 20.3% and 5.5% respectively in chronic obstructive pulmonary disease (COPD) patients and 5.5%, 14.8% and 1.85 respectively among interstitial lung disorder (ILD) patients; whereas the control cohort with no methyl isocyanate exposure displayed (CC, CT, and TT) cytosine, thymine as 2%, 1.6% and 2% respectively. Increased risk of Asthma among those carrying TT genotype and T allele (odds ratio [OR] =2.61 and 2.02 respectively). CONCLUSION: COPD risk significantly found among those with CC genotype and C allele (OR = 2.81 and 1.50 respectively), whereas ILD risk found significantly among CT genotype and C allele (OR = 1.75 and 1.40 respectively). Therefore, single nucleotide polymorphism (SNP) C-159T polymorphism in CD14 gene might be a risk factor for development of CLD in this population.

Hemorragia alveolar como complicación del uso de trombolíticos / Alveolar hemorrhage as a complication of thrombolytic therapy

La trombolisis se usa como estrategia de reperfusión coronaria en el infarto agudo de miocardio. El sangrado es su principal complicación; la mayoría ocurre en los sitios de accesos venosos y es leve, pero también pueden presentarse hemorragia gastrointestinal, retroperitoneal, genitourinaria, pulmonar y a nivel del sistema nervioso central, episodios estos generalmente de mayor gravedad y a veces fatales. Se describe aquí el caso de un paciente que recibió terapia trombolítica con estreptoquinasa como tratamiento por un infarto de miocardio, y que posteriormente desarrolló insuficiencia respiratoria aguda, infiltrados pulmonares bilaterales, caída del hematocrito y aumento de la difusión de monóxido de carbono, cuadro compatible con diagnóstico de hemorragia alveolar.

Coronary thrombolysis is used as a strategy for coronary reperfusion for acute myocardial infarction. Bleeding is the main complication described. Although most of these events occur at sites of vascular access and are mild, in some cases gastrointestinal, retroperitoneal, genitourinary, lung and central nervous system bleeding may occur. These episodes are usually serious and sometimes fatal. The following report describes the case of a patient who received thrombolytic therapy with streptokinase as a treatment for myocardial infarction. Subsequently he developed acute respiratory failure, bilateral pulmonary infiltrates and fall of hematocrit compatible with diagnosis of alveolar hemorrhage.

Efectos proinflamatorios de la contaminación atmosférica / Proinflammatory effects of air pollution in Santiago de Chile

Intermittent exposure of rats to Santiago's traffic pollution is associated to a decrease in growth after more than 100 days (range: 101-111) and to histological lung damage after 90 and particularly after 180 days. Our aim was to assess whether a 90 days exposure of rats to air from a Santiago's heavy traffic avenue, is able to induce a systemic proinflammatory reaction. Thirty-days-old Sprague-Dawley rats (n = 7) were directly exposed to air from a heavy traffic avenue (8 h, 5 days a week, from April 27 to July 29, 2009). Controls (n = 7) breathed animal room air. Rats were weighed twice a week and after completing 90 days of observation, lungs were subjected to histopathology and C reactive protein, viscosity and F2-isoprostane in plasma and microhematocrit were determined in blood samples. Exposure to PM10, PM2.5, ozone, NO2 and CO were estimated from registrations of 4 Santiago's monitoring stations. Plasmatic C reactive protein and viscosity and microhematocrit were significantly increased after 90 days of exposure as compared to controls (p < 0.05). No significant changes were observed in F2-isoprostane, nor in lung histopathology, nor in body weight curve versus time in exposed as compared to control series. Hourly mean value of PM25 in the 8 h of exposure was high: 38.9 ug/m³. It is concluded that 90 days of intermittent exposure of rats to Santiago's air pollution would promote a systemic inflammatory reaction. This response to air pollution might precede the decrease in body growth and the histological lung damage reported previously by our laboratory in the same species after intermittent Santiago's urban air pollution exposure.

La exposición intermitente de ratas centinela a la contaminación del tráfico vehicular de Santiago se ha asociado a disminución del crecimiento corporal después de cien días de exposición (rango: 101-111) y a daño histopatológico del pulmón a los 90 días y más, especialmente a los 180 días de exposición. Nuestro objetivo fue evaluar si la exposición al aire de una avenida con elevado tráfico vehicular durante 90 días era capaz de inducir en la rata una respuesta inflamatoria sistémica. Ratas Sprague-Dawley de 30 días de edad (n = 7) fueron directamente expuestas a respirar el aire de una avenida con elevado flujo vehicular (8 h, 5 días por semana, desde el 27 de abril hasta el 29 de julio de 2009). Las ratas control (n = 7) respiraron aire del bioterio. Las ratas se pesaron dos veces por semana y después de completar 90 días de observación, los pulmones se destinaron a estudio histopatológico. Se realizó microhematocrito y se determinó proteína C reactiva, viscosidad y F2-isoprostano plasmáticos en muestras de sangre. La exposición a PM10, PM2,5, ozono, NO2 y CO se calculó de los registros de cuatro estaciones de monitoreo de Santiago. Después de 90 días de exposición se observó un aumento significativo (p < 0,05) de la proteína C reactiva y de la viscosidad plasmática y también del microhematocrito, en relación a la serie control. No se observaron cambios significativos en F2-isoprostano plasmático, ni en la histopatología pulmonar, ni en la curva de peso corporal versus tiempo al comparar la serie expuesta con la serie control. El promedio horario de PM2,5 en las 8 horas de exposición fue alto: 38,9 ug/m³. Concluimos que 90 días de exposición intermitente a la contaminación aérea de Santiago en el modelo experimental promueve una reacción inflamatoria sistémica. Esta respuesta a la contaminación aérea podría preceder a la disminución del crecimiento corporal y al daño histológico pulmonar encontrado en otro de nuestros estudios en esta misma especie después...

Aerosol delivery of kinase-deficient Akt1 attenuates Clara cell injury induced by naphthalene in the lungs of dual luciferase mice

Conventional lung cancer therapies are associated with poor survival rates; therefore, new approaches such as gene therapy are required for treating cancer. Gene therapies for treating lung cancer patients can involve several approaches. Among these, aerosol gene delivery is a potentially more effective approach. In this study, Akt1 kinase-deficient (KD) and wild-type (WT) Akt1 were delivered to the lungs of CMV-LucR-cMyc-IRES-LucF dual reporter mice through a nose only inhalation system using glucosylated polyethylenimine and naphthalene was administrated to the mice via intraperitoneal injection. Aerosol delivery of Akt1 WT and naphthalene treatment increased protein levels of downstream substrates of Akt signaling pathway while aerosol delivery of Akt1 KD did not. Our results showed that naphthalene affected extracellular signal-regulated kinase (ERK) protein levels, ERK-related signaling, and induced Clara cell injury. However, Clara cell injury induced by naphthalene was considerably attenuated in mice exposed to Akt1 KD. Furthermore, a dual luciferase activity assay showed that aerosol delivery of Akt1 WT and naphthalene treatment enhanced cap-dependent protein translation, while reduced cap-dependent protein translation was observed after delivering Akt1 KD. These studies demonstrated that our aerosol delivery is compatible for in vivo gene delivery.

Acute accidental exposure to chlorine gas: Clinical presentation, pulmonary functions and outcomes.

Background. To study the clinical presentation, pulmonary functions and outcomes in subjects who were accidentally exposed to chlorine gas. Methods. Prospective observational study of 64 patients who sustained acute accidental exposure to chlorine gas during a leak in the chlorination system of the public bathing pool of a temple. Results. The major presenting symptoms and signs included acute dyspnoea (100%), chest discomfort (100%), cough (97%), eye irritation (88%), giddiness (72%), vomiting (46%), and heaviness in the head (44%); tachycardia (100%), tachypnoea (96%) and polyphonic wheezing (28%). All patients were managed in the emergency room with humidified oxygen inhalation and beta-2 agonist nebulisation and 52 were discharged within six hours. Twelve patients were severely affected and required hospitalisation; three of them were admitted into the intensive care unit. Three patients developed pulmonary oedema six to eight hours following admission. Pulmonary function testing (n=12) at presentation revealed obstructive defect in eight and mixed obstructive-cum-restrictive defect in four patients. The mean duration of hospital stay was 5.1±2.1 days. None of the patients died. Reactive airway dysfunction syndrome (RADS) was observed in three of the 12 hospitalised patients, who complained of manifested persistent cough that lasted for three months period following discharge. Serial pulmonary functions recovered to normal range by the end of the six months in all patients and remained so at one-year follow-up. Conclusion. Acute exposure to chlorine gas is an uncommon, but important public health hazard and can cause RADS, acute lung injury and pulmonary function abnormalities , which are reversible on prompt and appropriate management.

Pulmonary Toxicity after a Quick Course of Combinatorial Vincristine, Bleomycin, and Cisplatin Neoadjuvant Chemotherapy in Cervical Cancer

Pulmonary toxicity is one of the most serious adverse effects associated with a quick course of vincristine, bleomycin, and cisplatin neoadjuvant chemotherapy (NAC-VBP). The aim of this study was to evaluate pulmonary toxicity related to a quick course NAC-VBP. A total of consecutive 61 patients, who underwent at most 3 cycles of NAC-VBP every 10 days in the International Federation of Gynecology and Obstetrics (FIGO) stage IB-IIB cervical cancer from 1995 to 2007, were retrospectively analyzed. Of the 61 study subjects, 7 (11.5%) were identified to have pulmonary toxicity and 2 (3.3%) died of pulmonary fibrosis progression despite aggressive treatment and the use of a multidisciplinary approach. No factor predisposing pulmonary toxicity was identified. Initial symptoms were non-specific, but bronchiolitis obliterans organizing pneumonia and interstitial pneumonitis were characteristic findings by high-resolution computed tomography of the chest. The benefit of steroid therapy was uncertain and was associated with steroid-induced diabetes mellitus requiring insulin therapy in two patients. Fatal pulmonary toxicity is a major concern of a quick course NAC-VBP. In conclusion, these patients require special monitoring for bleomycin-induced pulmonary toxicity.

Effects of prone and supine position on oxygenation and inflammatory mediator in a hydrochloric acid-induced lung dysfunction in rats / Efeitos da posição prona e supina na oxigenação e mediador inflamatório na disfunção pulmonar induzida por ácido clorídrico em ratos

PURPOSE: To compare the effectiveness of mechanical ventilation of supine versus prone position in hydrochloric acid (HCl)-induced lung dysfunction. METHODS: Twenty, adult, male, Wistar-EPM-1 rats were anesthetized and randomly grouped (n=5 animals per group) as follows: CS-MV (mechanical ventilation in supine position); CP-MV (mechanical ventilation in prone position); bilateral instillation of HCl and mechanical ventilation in supine position (HCl+S); and bilateral instillation of HCl and mechanical ventilation in prone position (HCl+P). All groups were ventilated for 180 minutes. The blood partial pressures of oxygen and carbon dioxide were measured in the time points 0 (zero; 10 minutes before lung injury for stabilization), and at the end of times acid injury, 60, 120 and 180 minutes of mechanical ventilation. At the end of experiment the animals were euthanized, and bronchoalveolar lavages (BALs) were taken to determine the contents of total proteins, inflammatory mediators, and lungs wet-to-dry ratios. RESULTS: In the HCl+P group the partial pressure of oxygen increased when compared with HCl+S (128.0±2.9 mmHg and 111.0±6.7 mmHg, respectively) within 60 minutes. TNF-α levels in BAL do not differ significantly in the HCl+P group (516.0±5.9 pg/mL), and the HCl+S (513.0±10.6 pg/mL). CONCLUSION: The use of prone position improved oxygenation, but did not reduce TNF-α in BAL upon lung dysfunction induced by HCl.

OBJETIVO: Comparar os efeitos da ventilação mecânica em posição prona versus supina na disfunção pulmonar induzida por ácido clorídrico (HCl). MÉTODOS: Vinte ratos, adultos, Wistar-EPM-1 foram anestesiados e distribuídos aleatoriamente em grupos (n=5 animais por grupo): CS-MV (controle, ventilado mecanicamente em posição supina); CP-MV (controle, ventilado mecanicamente em posição prona); instilação bilateral de HCl e ventilação mecânica em posição supina (HCl+S) ou ventilação em posição prona (HCl+P). Todos os grupos foram submetidos a ventilação mecânica por 180 minutos. As pressões parciais de oxigênio e dióxido de carbono no sangue arterial foram mensuradas nos tempos Injúria ácida (10 minutos após instilação de HCl), e ao final de cada período após lesão por HCl, 60, 120 e 180 minutos sob ventilação mecânica. Ao final do experimento os animais foram eutanasiados, os pulmões retirados para avaliação do peso úmido em relação ao peso seco do pulmão direito e realizamos o lavado broncoalveolar (BAL) para determinação de proteínas totais e o mediador inflamatório TNF-α. RESULTADOS: No grupo HCl+P a pressão parcial de oxigênio, no tempo de 60 minutos, aumentou quando comparada com o grupo HCl+S (128.0±2.9 e 111.0±6.7 mmHg, respectivamente). Os níveis de TNF-α no lavado broncoalveolar não diferiram de maneira estatisticamente significante quando comparamos os grupos HCl+S (513.0±10.6 pg/mL) versus HCl+P (516.0±5.9 pg/mL). CONCLUSÃO: O uso da posição prona melhora a oxigenação, mas não reduz os níveis de BAL após disfunção pulmonar induzida por HCl.

Aluminio en el tracto respiratorio bajo de residentes de la Ciudad de México / Aluminium in the lower respiratory tract of people living in México City

Objetivo Se investigó la presencia de aluminio (Al) y de patologías respiratorias en el tracto respiratorio bajo de personas que habían residido en Ciudad de México por un tiempo mínimo de dos años. Métodos Se obtuvo 250 muestras de tejido respiratorio (lóbulos pulmonares, nódulo linfático peribronquial, bronquios e hilio), durante la autopsia médico legal de 36 individuos. Para la cuantificación de Al se utilizó plasma de inducción acoplado (ICP -OES) a la espectrofotometría de absorción atómica previo a lo cual las muestras fueron sometidas a un proceso de secado, trituración y digestión. Resultados Se identificaron 13 diferentes patologías, solo tres de ellas: enfisema pulmonar, bronquitis y antracosis, se correlacionan con la presencia de Al, elemento distribuido en concentraciones muy variables (rango:2,7 a 836,1 microgramos de Al por gramo de tejido seco (ì g Al/g ts). En lóbulos, bronquios e hilio la cantidad de Al encontrada fue mucho menor que la encontrada en nódulos peribronquiales, siendo la diferencia estadísticamente significativa. El análisis multivariado por conglomerados mostró que la muestra estaba conformada por tres clases de individuos, agrupados de acuerdo a la cantidad y distribución del Al en el tracto respiratorio bajo, a la edad, tiempo de residencia en la ciudad de México y presencia de patologías. Conclusión Se postula que el Al encontrado en el tracto respiratorio bajo de residentes de ciudad de México proviene del aire; la cantidad y el patrón de distribución dependen del tiempo y del lugar de residencia y al depositarse puede provocar enfermedades respiratorias.

Objective Investigating the presence of aluminium (Al) and respiratory pathologies in the lower respiratory tract of people who had lived in Mexico City for a minimum of two years. Methods 250 respiratory tissue samples were obtained from pulmonary lobes, lymph nodes, bronchial and hilum regions during 36 individuals' autopsies. Inductively coupled plasma optical emission spectrometry (ICP-OES) was used for quantifying Al; the samples has been previously dried, ground and digested. Results 13 different pathologies were identified but only three of them (pulmonary emphysema, bronchitis and anthracosis) were correlated with the presence of Al, an element being distributed in very variable concentrations (range: 2,7 to 836,1 micrograms of Al per gram of dry tissue (ì g Al/g ts)). The amount of Al found in lobes, bronchial and hilum regions was much smaller than that found in lymph nodes; such difference was statistically significant. Multivariate analysis by conglomerates revealed that the sample consisted of three classes of individuals, grouped according to the amount and distribution of Al in the lower respiratory tract, age, time spent living in Mexico City and the presence of pathologies. Conclusions The Al found in the lower respiratory tract of residents of Mexico City would thus seem to have come from the air. The amount of Al and its distribution pattern depended on the time and place of residence and can lead to respiratory illness.

Complicações pulmonares após uso de crack: achados na tomografia computadorizada de alta resolução do tórax / Pulmonary complications of crack cocaine use: high-resolution computed tomography of the chest

Relatamos os achados na tomografia computadorizada de alta resolução de um paciente que, após uso de cocaína fumada (crack), desenvolveu quadro de hemoptise, dispnéia e dor torácica súbitas. As radiografias de tórax mostravam consolidações predominando em lobos superiores. A tomografia de alta resolução evidenciava opacidades em vidro fosco, consolidações e nódulos do espaço aéreo. Nova tomografia de controle, após suspensão da droga e uso de corticóides, mostrou regressão parcial das lesões e aparecimento de escavações. A correlação entre os achados clínicos, laboratoriais e de imagem permitiu o diagnóstico de "pulmão de crack".

Here, we report high-resolution computed tomography (HRCT) findings in a patient who developed sudden hemoptysis, dyspnea and chest pain after smoking crack cocaine. Chest X-rays showed consolidations, primarily in the upper lobes, and HRCT scans showed ground glass attenuation opacities, consolidations and air-space nodules. A follow-up CT, after drug use discontinuation and administration of corticosteroids, showed partial resolution of pulmonary lesions and the appearance of cavitations. Clinical, imaging and laboratory findings led to a diagnosis of 'crack lung'.

Intratracheal Administration of Endotoxin Attenuates Hyperoxia-Induced Lung Injury in Neonatal Rats

PURPOSE: This study was undertaken to determine the effects of intratracheal administration of endotoxin on hyperoxia-induced lung injury in neonatal rats. MATERIALS AND METHODS: Newborn Sprague Dawley rat pups were divided into four experimental groups: normoxia control (NC), normoxia with endotoxin treatment (NE), hyperoxia control (HC), and hyperoxia with endotoxin treatment (HE) groups. In HC and HE, rat pups were subjected to 14 days of hyperoxia (> 95% oxygen) within 12 hours after birth. In endotoxin treated group (NE and HE), Escherichia coli endotoxin (0.5microgram in 0.03mL of saline) was given intratracheally at the 1st, 3rd and 5th postnatal day. Radial alveolar count (RAC), mean linear intercept (MLI), RAC/MLI ratios, and degree of fibrosis were measured to assess the changes in lung morphology. RESULTS: During the research period, survival rates in both HC and HE were notably reduced 7 days after endotoxin was administered, but body weight gain was considerably reduced only in HC. On day 14, significant arrest in alveolarization, as evidenced by the decrease of RAC and RAC/MLI ratio and increase of MLI as well as increased fibrosis, were noted in HC. Although slight but significant arrest in alveolarization and increased fibrosis score were observed in NE compared to NC, the hyperoxia-induced lung damage observed in HC was significantly improved in HE. CONCLUSION: This study suggests that intratracheal administration of endotoxin significantly attenuated hyperoxia-induced lung injury in neonatal rats.