Topiramate Reduces Aortic Cross-Clamping-Induced Lung Injury in Male Rats.

BACKGROUND: Topiramate (TPM) decreases cytokine release and generation of reactive oxygen species (ROS). Cytokine and endothelin-1 (ET-1) secretion and ROS formation play an important role in ischemia-reperfusion (I/R) injury. We aimed to evaluate whether TPM prevents damage occurring in lung tissue during I/R. MATERIALS AND METHODS: A total of 27 Wistar albino rats were divided into three groups of nine. To the I/R group, two hours of ischemia via infrarenal abdominal aorta cross-ligation and then two hours of reperfusion process were applied. TPM (100 mg/kg/day) orally for seven days was administered in the TPM treatment group. After the last dose of TPM treatment, respectively, two hours of ischemia and two hours of reperfusion were applied in this group. RESULTS: Tumor necrosis factor-alpha (TNF-α) (p < 0.05), malondialdehyde (MDA) (p < 0.05), myeloperoxidase (MPO) (p < 0.05) and ET-1 (p < 0.05) levels of TPM treatment group's lung tissue were significantly lower than for the I/R group. Caspase-3 and histopathological damage were rather lower than that of the I/R group. CONCLUSIONS: During I/R, lung damage occurs due to excessive TNF-α and ET-1 release and ROS generation. TPM could well reduce development of lung damage by decreasing cytokine and ET-1 release and levels of ROS produced.

Mediastinitis and subcutaneous abscess complicated after EBUS-TBNA of 2R mediastinal lymph node.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUSTBNA) is a minimally invasive diagnostic tool used for the evaluation of mediastinal lymphadenopathy. It is a safe procedure, but complications such as bleeding and infection may occur. We report a case of a patient who developed a subcutaneous abscess abscess and mediastinitis after EBUSTBNA. A 75-year-old male with a history of right nephrectomy due to renal cell carcinoma and lung adenocarcinoma history underwent EBUS-TBNA for the evaluation of a right upper paratracheal lymph node. Two weeks after the procedure, the patient presented to the emergency department with skin induration and erythema on the right clavicular area. A non-contrast neck and thorax CT scan was performed, which revealed an extensive subcutaneous abscess on the right clavicular area, extending to the supraclavicular region. The patient was hospitalized, and empirical intravenous antibiotics were initiated due to deep neck infection. Repeated drainage of the subcutaneous abscess was performed. Bacteriologic examination revealed Streptococcus mitis. The patient showed improvement with antibiotic treatment, and a follow-up ultrasound showed a decrease in the size of the abscess and was discharged approximately four weeks after hospitalization. Although very rare, serious infectious complications may develop after EBUSTBNA, and our case report is an important example regarding its management process.

The effect of rocuronium, sugammadex, and their combination on cardiac muscle and diaphragmatic skeletal muscle cells.

PURPOSE: Rocuronium has been associated with muscle weakness when administered in prolonged infusions. The effect of sugammadex and rocuronium together on muscle is unknown. In this study, we examined the effects of rocuronium and sugammadex, and the complex formed by these agents, on cardiac and diaphragmatic muscle cells. METHODS: Forty-two Sprague-Dawley male rats were divided into six groups. Group I received only rocuronium at a dose of 1 mg/kg and groups II and III received sugammadex alone at doses of 16 and 96 mg/kg, respectively. Groups IV and V received 1 mg/kg rocuronium plus 16 mg/kg sugammadex and 1 mg/kg rocuronium plus 96 mg/kg sugammadex, respectively. Group six was the control group and received only 0.9 % NaCl without any drug. RESULTS: Histopathological examination demonstrated that rocuronium and high doses of sugammadex accumulated in both cardiac and diaphragm muscle tissues. We also observed intense edema and degeneration in diaphragmatic and myocardial cells when the rocuronium-sugammadex complex was used. Rocuronium and sugammadex remain in the circulation for a long time and they may cause skeletal muscle myopathy, vacuolization, pyknotic nuclear clumps, and hypertrophy, and weaken the muscle fibers. CONCLUSION: Rocuronium, sugammadex, and rocuronium-sugammadex complexes cause histopathological changes and immunoreactivity to calcineurin in muscle cells.

Management of primary spontaneous pneumothorax: Our single-center, five-year experience.

Background: In this study, we aimed to analyze the effects of admission time to the hospital and different variables on the treatment efficiency and to evaluate the recurrence during the clinical management process in patients with the diagnosis of primary spontaneous pneumothorax. Methods: A total of 149 patients with primary spontaneous pneumothorax (131 males, 18 females; mean age: 24.8±6.8 years; range, 17 to 35 years) treated in our clinic between January 2015 and December 2019 were retrospectively analyzed. Time from symptom onset to hospital admission (admission time) was classified as three periods: <24 h, between 24 and 72 h, and >72 h. Data including admission time, demographic and clinical characteristics, smoking history, body mass index, the use of pleurectomy or pleural abrasion during surgery were collected from the charts of the patients. Results: Admission time had no statistically significant effect on the length of hospital stay, recurrence, and the need for surgery. Male sex, smoking history, and lower body mass index had no significant effect on the recurrence. Recurrence and length of hospital stay did not significantly differ between the patients in whom pleurectomy or pleural abrasion added to the procedure during the operation. Conclusion: A longer interval between symptom onset and hospital admission and lower body mass index have no adverse effect on treatment outcomes and the recurrence in patients with primary spontaneous pneumothorax. Despite the fact that surgical treatment significantly decreases the recurrence rate, pleurectomy and pleural abrasion techniques have no significant difference on the clinical influence and recurrence of these patients.

The influence of specific factors on postoperative morbidity in young adults with bronchiectasis.

BACKGROUND: Surgical treatment of bronchiectasis is associated with acceptable mortality and morbidity rates. To date, few reports on the prediction of postoperative morbidity using some preoperative measures have been presented. We present our results regarding the influence of some specific factors on postoperative morbidity on young adult patients who were treated surgically for bronchiectasis. METHODS: Between January 2000 and July 2007, 122 patients were operated upon. Female gender, increased number of resected segments, presence of haemoptysis and bilateral disease, compromised pulmonary function test (FEV1/VC<60%) and absence of preoperative fiberoptic bronchoscopy (FOB) were examined as the potential risk factors for postoperative complications such as persistent air leak (PAL), atelectasis, residual air space (RAS), bronchopleural fistula (BPF) and empyaema. RESULTS: There was no operative mortality. Morbidity was observed in a total of 16 patients with an overall morbidity rate of 13.1%. Complete resection was achieved in 88 patients (72.1%). The number of resected segments was not found to be significantly associated with increased morbidity. Presence of preoperative haemoptysis did not correlate with postoperative complications significantly. Absence of preoperative FOB was not found to be associated with post-operative complications (p<0.05). Compromised PFT was significantly associated with RAS (p=0.028), however it was not associated with increased risk of PAL, atelectasis or empyaema significantly. CONCLUSION: Multi-segmental resectable bronchiectasis should not be considered an occult risk factor for morbidity after resection. Associated non-severe haemoptysis and absence of preoperative bronchoscopy are not associated with significant increased risk of postoperative morbidity.

Sleeve resections for squamous cell carcinoma of the lung.

BACKGROUND: Sleeve resection is an advanced technique that was developed as an alternative to pneumonectomy. This study evaluated our cases of sleeve resection for squamous cell carcinoma of the lung and compared the outcomes with the literature reports. METHODS: In total, 26 bronchial, 5 bronchovascular, and 3 vascular sleeve lobectomies were performed between January 2000 and July 2005 in our clinic. Age, gender, operations, postoperative diagnosis and staging, and postoperative morbidity and mortality were evaluated. RESULTS: Sleeve resections were performed in 34 patients. All patients were male, with a mean age of 59.4 years. The operations consisted of 16 right upper, 14 left upper, and 1 left lower sleeve lobectomies and 3 superior sleeve bilobectomies. The most common postoperative pathological staging group was stage IIb (32.3%). Operative mortality was 5.9% (n=2). Postoperative morbidity was 20.5% (n=7), including 4 prolonged air leaks plus empyema, 1 prolonged air leak, 1 postoperative bleeding needing revision, and 1 severe bronchostenosis; of these, 6 had persistent atelectasis. The local tumour recurrence rate was 11.7% (n=4). The median survival time and 5-year survival were 36 months and 42%, respectively. CONCLUSIONS: Sleeve resection proved to be good therapy for lung cancer and has a lower morbidity and mortality than standard pneumonectomies and results in better lung function and quality of life. The anastomosis-related complications are experience-related technical complications and training thoracic surgeons to perform SRs at experienced centres will reduce the morbidity associated with SRs.

Zinc aspartate alleviates lung injury induced by intestinal ischemia-reperfusion in rats.

BACKGROUND: Intestinal ischemia-reperfusion (II/R) induced acute lung injury is mediated by activated neutrophils and formation of free radicals. Several antioxidants have been shown to attenuate such remote organ injury. We studied the effects of zinc aspartate on lung injury induced by II/R in rats. MATERIALS AND METHODS: Twenty-four Sprague-Dawley rats were randomized into three groups. Group I was the control. Animals in Groups II and III (II/R + zinc aspartate [ZA]) underwent 60 min of ischemia and 60 min of reperfusion, respectively. Rats in Group III also received 50 mg/kg zinc aspartate before 15 min of reperfusion. Lung tissue samples and bronchoalveolar lavage fluid were obtained to assess lung tissue myeloperoxidase (MPO), adenosine deaminase (ADA), xanthine oxidase (XO), glutathione peroxidase (GPx) activities, and nitric oxide (NO), malondialdehyde (MDA) levels. Also, the levels of MDA, NO, and MPO activity were determined in bronchoalveolar lavage fluid. RESULTS: Compared with the control, lung tissue MDA, NO levels, and MPO, ADA, XO activities were markedly increased (P < 0.05), whereas GPx activity significantly decreased in the II/R group (P < 0.05). However, administration of ZA significantly reversed these effects by reducing the levels of MDA, NO, and decreasing MPO, ADA, XO activities (P < 0.05). In addition, ZA significantly increased GPx activity (P < 0.05). The activity of MPO and the levels of NO and MDA were found to be higher in bronchoalveolar lavage fluid in II/R group than the control (P < 0.05). Zinc aspartate significantly diminished MPO activity and the levels of NO and MDA compared with that of control rats (P < 0.05). CONCLUSION: Our results indicate that zinc aspartate alleviates lung injury induced by II/R attributable to its antioxidant and antiinflammatory effects.

Diffuse cystic disease of the lung associated with simultaneous bilateral spontaneous pneumothorax: an unknown component of Caroli disease?

Simultaneous bilateral spontaneous pneumothorax is an uncommon and serious medical problem frequently related to an underlying lung disease such as parenchymal lung disease, inflammatory events or neoplasms. Recurrent pneumothorax associated with persistent air leakage may pose a therapeutic dilemma in patients with underlying lung diseases. Caroli disease (CD) is a very rare congenital disorder characterised by intrahepatic biliary cystic dilatations and frequently associated with polycystic kidney and hepatic fibrosis. To date, no relation between CD and the bilateral diffuse cystic structure of pulmonary parenchyma has been described. In this paper we present a patient with the diagnosis of CD in whom simultaneous bilateral spontaneous pneumothorax was the initial finding due to severe underlying pulmonary disease. Our patient's demographic and clinical characteristics, laboratory findings and course made us exclude the other aetiologies leading to such diffuse multi-bullous pulmonary involvement. The coincidence of recurrent pneumothorax and severe pulmonary disease has led to a big therapeutic dilemma. Open or minimally invasive surgery could be morbid or even mortal because of the nature of the parenchyma and the operative risk due to CD. Therefore, we suggest a unique conservative management including tube thoracostomy by locating the correct air spaces with the aid of high-resolution computed tomography followed by talc pleurodesis in patients with severe multi-bullous lung disease associated with potential risks due to co-morbidities.

Diffuse cystic bronchiectasis associated with left microtia and external auditory canal atresia: a very rare coincidence.

OBJECTIVE: To present a case in which diffuse cystic bronchiectasis was associated with left microtia/external auditory canal atresia. CLINICAL PRESENTATION: A 10-year-old girl suffering from cough, fever, dyspnea and sputum for 6 months was transferred to our clinic due to the diagnosis of bronchopneumonia. She had recurrent episodes of bronchopneumonia. On examination, left microtia and left external auditory canal atresia were detected. Thorax CT revealed diffuse cystic bronchiectasis on the left lung. Radiological examination showed atresia of the left external auditory canal. We could not find any etiopathological reason causing bronchiectasis. INTERVENTION: The patient underwent left pneumonectomy and postoperative histopathology was reported as bronchiectasis. CONCLUSION: This report shows a unique case in which an association of diffuse cystic bronchiectasis and left microtia/external auditory canal atresia was observed. Hence in newborns with microtia and/or external auditory canal atresia, the probability of development of bronchiectasis should be borne in mind and such patients should be followed up more carefully regarding this rare association.

Surgical management of bronchiectasis in childhood.

OBJECTIVE: Though there is a gradual decrease in the prevalence of bronchiectasis, it is still a cause of mortality and morbidity among children in developing countries such as Turkey. We reviewed the morbidity and mortality rates and the outcome of surgical treatment for childhood bronchiectasis. PATIENTS AND METHODS: Age, sex, etiological factors, symptoms, radiological examinations, surgical procedures, postoperative morbidity and mortality in patients aged 16 years and younger, operated for bronchiectasis between January 1991 and April 2006 in the Thoracic Surgery Clinic of Atatürk Training and Research Hospital for Chest Disease and Chest Surgery were reviewed retrospectively. RESULTS: Between January 1991 and April 2006, 176 cases aged 16 and younger were operated for bronchiectasis. There were 95 females (54%) and 81 males (46%), with a mean age of 12.3 years (range: 3.4-16 years). The most common cause of bronchiectasis was lung infection (n: 87, 49.4%). Main symptoms were coughing (n: 167, 94.9%), sputum (n: 139, 79%), hemoptysis (n: 78, 44.3%), and fever (n: 77, 43.7%). Mean duration of the symptoms in patients who were operated was 3.8 years (range: 0-7.6 years). Cases underwent a total of 201 operations: 19 cases had bilateral surgical resection and 6 cases had completion pneumonectomy. Majority of cases had complete resection (n: 165, 93.75%) while only 11 cases (6.25%) had incomplete resection. Mean duration of hospitalization was 8.9 days (range: 5-39 days). The outcome, based on the responses of patients postoperatively, was 'perfect' in 129 cases (73.3%), 'improved' in 41 cases (23.3%), and 'no changes' in 6 cases (3.4%). The mean follow-up after surgery was 4.3 years (range: 14 months to 7.2 years), mortality was 0% and morbidity was 13% (n: 23). CONCLUSION: With acceptable mortality and morbidity rates and high chance of cure after complete resection, surgical treatment is a successful and reliable method of treatment in childhood bronchiectasis that yields marked improvement in the quality of life.

Primary pulmonary mucinous adenocarcinoma in a 15-year-old boy.

Bronchogenic carcinomas are rare in childhood. Furthermore, mucinous (so-called colloid) adenocarcinoma, an unusual variant of pulmonary adenocarcinoma, is extremely rare in the first decade of life. To the best of our knowledge, we report the first case with primary pulmonary mucinous adenocarcinoma at the age of 15. Another interesting aspect of this tumor was its metastasis to thyroid, because metastasis of primary bronchogenic carcinomas to thyroid is uncommon. One can face up with difficulties in the establishment of the definite diagnosis due to its complex and often indistinguishable histopathologic pattern. In this paper we report a patient with pulmonary solid mass and thyroid nodule, initially diagnosed as metastatic thyroid carcinoma in whom postoperative resective surgery confirmed primary pulmonary mucinous adenocarcinoma with synchronous metastasis to thyroid.

Successful conservative management of Boerhaave's syndrome with late presentation.

In this report, we describe the diagnostic, clinical and therapeutic aspects of a 22-year-old man who was diagnosed with a case of Boerhaave's syndrome (BS) 86 hours after acute onset of chest pain and dyspnea following forceful vomiting due to excessive ingestion of alcohol. Early diagnosis and prompt treatment is critical in BS due to the high mortality rates related to delay in diagnosis. We think the main criterion of prognosis is not only the free interval between diagnosis and treatment but the clinical form. We suggest conservative management, including intrathoracic lavage and close monitoring in patients with late presentation with a distal esophageal tear.

Investigation of surfactant protein-D and interleukin-6 levels in patients with blunt chest trauma with multiple rib fractures and pulmonary contusions: a cross-sectional study in Black Sea Region of Turkey.

OBJECTIVE: Multiple rib fractures (RFs) and pulmonary contusions (PCs), with resulting systemic lung inflammation, are the most common injuries caused by blunt chest trauma (BCT) in motor vehicle accidents. This study examined levels of the inflammation marker interleukin (IL)-6 and those of the acute-phase reactant surfactant protein (SP)-D in patients with BCT. DESIGN: Prospective, cross-sectional, observational study. SETTING: Single-centre, tertiary care hospital in the Black Sea Region of Turkey. PARTICIPANTS: The study included 60 patients with BCT who were hospitalised in our thoracic surgery department. PARAMETERS MEASURES: The SP-D and IL-6 serum levels of patients with RFs (two or more RFs) (n=30) and patients with PCs (n=30) were measured after 6 hours, 24 hours and 7 days, and compared with those of age-matched and gender-matched healthy participants. RESULTS: The 6-hour serum SP-D levels of the RFs (p=0.017) and PCs (p<0.001) groups were significantly higher than those of the healthy controls. The 24-hour and 7-day SP-D levels of both groups were also higher than the control group. The serum IL-6 levels of both groups were significantly higher than those of the control group. We have found Injury Severity Score to be independently related to 6-hour IL-6 (ß=1.414, p<0.001) and 24-hour IL-6 levels (ß=1.067, p<0.001). The development of complications was independently related to 6-hour SP-D level (ß=0.211, p=0.047). CONCLUSIONS: RFs and PCs after BCT lead to local and systemic inflammation due to lung injury. The levels of the systemic inflammation marker IL-6 and those of the acute-phase reactant SP-D were elevated in the present study. The SP-D level may be used as a marker in the follow-up of BCT-related complications.

The protective effect of infliximab against carbon tetrachloride-induced acute lung injury.

OBJECTIVES: Carbon tetrachloride (CCl4) causes pulmonary toxicity. Infliximab (Ib) is a potent inhibitor of tumor necrosis factor-alpha (TNF-α). We aimed to investigate whether Ib has a protective effect on CCl4 induced lung injury. MATERIALS AND METHODS: Rats were divided into control, CCl4, and CCl4+Ib groups. A single dose of 2 ml/kg CCI4 was administered to CCI4 group and a single dose of 7 mg/kg Ib was given to CCl4+Ib group 24 hr before applying CCI4. RESULTS: TNF-α, malondialdehyde (MDA), nitric oxide (NO) and caspase-3 levels of the CCl4 group were markedly higher than both the control and CCl4+Ib groups. The CCI4+Ib group had lower histopathological injury than the CCl4 group. CONCLUSION: Ib as a strong TNF-α blocker decreases the production of proinflammatory cytokines, MDA, and oxidative stress leading to a protective effect against CCl4 induced lung tissue injury.

Is adalimumab protective in ischemia-reperfusion injury in lung?

OBJECTIVES: Increasing cytokines and reactive oxygen species (ROS) during ischemia reperfusion (I-R) leads to the lung damage. Adalimumab (Ada) is a potent tumor necrosis factor-alpha (TNF-α) inhibitor agent. We aimed to evaluate whether Ada would prevent the lung tissue from damage development over the I-R process. MATERIALS AND METHODS: Twenty seven Wistar albino male rats were divided into three groups (each group had 9 rats). To the control group, only laparotomy procedure was carried out. For I-R group, first infrarenal abdominal aorta was cross-clamped during 2 hr, and then reperfusion was performed for 2 hr. To I-R+Ada group, first a single dose of 50 mg/kg Ada was given intraperitoneally and 5 days later, same I-R procedure was carried out. RESULTS: Levels of TNF-α, malondialdehyde (MDA), myeloperoxidase (MPO), endothelin-1 (ET-1) and caspase-3 enzyme activity of I-R group were higher than that of both I-R+ Ada [TNF-α (P=0.021), MDA (P=0.029), MPO (P=0.012), ET-1 (P=0.036, caspase-3 (P=0.007), respectively] and control group [TNF-α (P=0.008), MDA (P<0.001), MPO (P=0.001), ET-1 (P<0.001), caspase-3 (P<0.001), respectively]. In I-R group, severe damage was detected by hematoxylin-eosin staining. This damage was found less severe in Ada treatment group. CONCLUSION: The release of cytokines and ET-1 in a large proportion after I-R injury, and generating of ROS in excessive quantity could cause severe damage in the lung tissue. Ada could be considered as a protective agent for lung tissue during I-R process.

Protective Effects of Infliximab on Lung Injury Induced by Methotrexate.

INTRODUCTION: Methotrexate (MTX) is used to treat cancers, several forms of arthritis and other rheumatic conditions, although MTX may cause pulmonary toxicity related to the production of free oxygen radicals, various cytokines. Infliximab (IB) with its potent effect on tumor necrosis factor-alpha (TNF-α) inhibition also inhibits the release of endothelin-1 (ET-1). We aimed to investigate whether IB reduces pulmonary damage induced by an overdose of MTX. METHOD: The rats were divided into 3 groups of 8 animals. The control group was given only saline. One dose of 20mg/kg MTX intraperitoneal was administered in the MTX group. IB 7 mg/kg was given to the MTX+IB (MI) group. Three days after IB was administered, 20mg/kg MTX was given. Five days after MTX was administered, all rats were sacrificed. RESULTS: The TNF-α, ET-1, malondialdehyde (MDA), myeloperoxidase (MPO) and caspase-3 levels in MTX group were significantly higher than in control groups of TNF-α (P=.001), ET-1 (P=.001), MDA (P=.001), MPO (P=.001) and caspase-3 levels (P=.001) and MI groups of TNF-α (P=.009), ET-1 (P=.001), MDA (P=.047), MPO (P=.007) and caspase-3 levels (P=.003). The MI group had less histopathological damage in lung tissue than the MTX group. CONCLUSION: Overdose of MTX leads to cytokine release and the formation of reactive oxygen species in addition to increased ET-1 secretion release that causes lung damage. IB, as a potent proinflammatory agent, TNF-α blocker, can decrease ET-1 release and oxidative stress, it may show significant protective effects in lung tissue against damage caused by MTX overdose.

A comprehensive analysis of traumatic rib fractures: morbidity, mortality and management.

OBJECTIVE: A rib fracture secondary to blunt thoracic trauma is an important indicator of the severity of the trauma. In the present study we explored the morbidity and mortality rates and the management following rib fractures. METHODS: Between May 1999 and May 2001, 1417 cases who presented to our clinic for thoracic trauma were reviewed retrospectively. Five hundred and forty-eight (38.7%) of the cases had rib fracture. There were 331 males and 217 females, with an overall mean age of 43 years (range: 5-78 years). These patients were allocated into groups according to their ages, the number of fractured ribs and status, i.e. whether they were stable or unstable (flail chest). RESULTS: The etiology of the trauma included road traffic accidents in 330 cases, falls in 122, assault in 54, and industrial accidents in 42 cases. Pulmonary complications such as pneumothorax (37.2%), hemothorax (26.8%), hemo-pneumothorax (15.3%), pulmonary contusion (17.2%), flail chest (5.8%) and isolated subcutaneous emphysema (2.2%) were noted. 40.1% of the cases with rib fracture were treated in intensive care units. The mean duration of their stay in the intensive care unit was 11.8+/-6.2 days. 42.8% of the cases were treated in the wards whereby their mean duration of hospital stay was 4.5+/-3.4 days, while 17.1% of the cases were followed up in the outpatient clinic. Twenty-seven patients required surgery. Mortality rate was calculated as 5.7% (n=31). CONCLUSIONS: Rib fractures can be interpreted as signs of significant trauma. The greater the number of fractured ribs, the higher the mortality and morbidity rates. Patients with isolated rib fractures should be hospitalized if the number of fractured ribs is three or more. We also advocate that elderly patients with six or more fractured ribs should be treated in intensive care units due to high morbidity and mortality.

An unusual radiological presentation of a pulmonary hydatid cyst in a child.

Giant pulmonary hydatid cyst is usually encountered in adolescents and children who are older than 10 years. A relatively higher elasticity of the lung tissue allows rapid growth of cysts. We present a case of a 15-year-old male who was admitted with complaint of frequent and persistent dry cough for over a month. Computed tomographic scan revealed a giant cyst with thick enhancing rim and an "air bubble" sign. Diagnosis of giant hydatid cyst was confirmed by surgery and histopathological examination.

Efectos protectores de infliximab sobre el daño pulmonar inducido por metotrexato / Protective Effects of Infliximab on Lung Injury Induced by Methotrexate

Introducción: El metotrexato (MTX) se emplea para tratar el cáncer, varias formas de artritis y otras patologías reumáticas, pero puede causar toxicidad pulmonar debido a la producción de radicales libres del oxígeno y varias citocinas. Infliximab (IB) es un potente inhibidor del factor de necrosis tumoral-alfa (TNF-alfa) e inhibe también la liberación de endotelina-1 (ET-1). Nos propusimos investigar si IB reduce el daño pulmonar inducido por una sobredosis de MTX. Método: Las ratas se dividieron en 3 grupos de 8 animales. Al grupo control solamente se le administró solución salina. Al grupo MTX se le administró una dosis intraperitoneal de 20 mg/kg de MTX. Al grupo de MTX + IB (MI) se le administraron 7 mg/kg de IB. Tres días después de la administración de IB se administraron 20mg/kg de MTX. Todas las ratas se sacrificaron 5días después de la administración de MTX. Resultados: Las concentraciones de TNF-alfa, ET-1, malondialdehído (MDA), mieloperoxidasa (MPO) y caspasa-3 fueron significativamente más altas en el grupo MTX que en el grupo control: TNF-alfa (p < 0,001), ET-1 (p < 0,001), MDA (p < 0,001), MPO (p < 0,001) y caspasa-3 (p < 0,001) y en el grupo MI: TNF-alfa (p < 0,009), ET-1 (p < 0,001), MDA (p < 0,047), MPO (p < 0,007) y caspasa-3 (p < 0,003). El grupo MI mostró menos daño histopatológico en el tejido pulmonar que en el grupo MTX. Conclusión: La sobredosis de MTX induce la liberación de citocinas y la formación de especies reactivas de oxígeno, además de una mayor secreción de ET-1 que provoca daño pulmonar. IB es un agente proinflamatorio potente, bloquea el TNF-alfa, puede reducir la liberación de ET-1 y el estrés oxidativo y mostrar importantes efectos protectores del tejido pulmonar frente al daño causado por una sobredosis de MTX

Introduction: Methotrexate (MTX) is used to treat cancers, several forms of arthritis and other rheumatic conditions, although MTX may cause pulmonary toxicity related to the production of free oxygen radicals, various cytokines. Infliximab (IB) with its potent effect on tumor necrosis factor-alpha (TNF-alfa) inhibition also inhibits the release of endothelin-1 (ET-1). We aimed to investigate whether IB reduces pulmonary damage induced by an overdose of MTX. Method: The rats were divided into 3 groups of 8 animals. The control group was given only saline. One dose of 20 mg/kg MTX intraperitoneal was administered in the MTX group. IB 7 mg/kg was given to the MTX + IB (MI) group. Three days after IB was administered, 20 mg/kg MTX was given. Five days after MTX was administered, all rats were sacrificed. Results: The TNF-α, ET-1, malondialdehyde (MDA), myeloperoxidase (MPO) and caspase-3 levels in MTX group were significantly higher than in control groups of TNF- alfa (P = .001), ET-1 (P = .001), MDA (P = .001), MPO (P = .001) and caspase-3 levels (P = .001) and MI groups of TNF-alfa (P=.009), ET-1 (P = .001), MDA (P = .047), MPO (P = .007) and caspase-3 levels (P = .003). The MI group had less histopathological damage in lung tissue than the MTX group. Conclusion: Overdose of MTX leads to cytokine release and the formation of reactive oxygen species in addition to increased ET-1 secretion release that causes lung damage. IB, as a potent proinflammatory agent, TNF-alfa blocker, can decrease ET-1 release and oxidative stress, it may show significant protective effects in lung tissue against damage caused by MTX overdose

Effects of early administration of dexamethasone, N-acetylcysteine and aprotinin on inflammatory and oxidant-antioxidant status after lung contusion in rats.

INTRODUCTION: This experimental setting was undertaken to elucidate and confirm the role of inflammatory and oxidant-antioxidant mechanisms on blunt injury induced moderate pulmonary contusion (PC). We intended to determine the effects of dexamethasone (DXM), N-acetylcysteine (NAC) and aprotinin (APR) in terms of their ability to diminish the consequences of acute lung injury due to PC. METHODS: Rats were allocated to five subgroups. Except for the control, all subgroups had a moderate pulmonary contusion. Following 45 min of observation, animals in groups I and II received intraperitoneal saline, group III 10 mg/kg DXM, group IV 500 mg/kg NAC and group V 30,000 kIU/ml APR. After the procedure, 6 h after contusion, blood gas analysis, lung tissue nitric oxide (NO) and malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activity, bronchoalveolar lavage (BAL) fluid and histopathological examination were performed. RESULTS: All PaO(2) values decreased significantly in contused rats as compared with the control group (p<0.05). DXM, NAC and APR resulted in a slight increase in PaO(2) values compared with group II (p<0.05). Lung tissue levels of MDA and NO were higher in the contusion group than in the control (p<0.05). DXM, NAC and APR all decreased the levels of MDA and NO (p<0.05), however the decrease in NO was not found to be significant with APR (p>0.05). SOD and CAT activities increased significantly after contusion compared to control group (p<0.05). There was no significant difference even though SOD levels were elevated in groups III, IV and V compared with contused animals (p>0.05). Neutrophils in BAL fluid significantly increased in contused animals (p<0.05). Only DXM significantly decreased neutrophil population in BAL fluid (p<0.05). Scores for alveolar haemorrhage/oedema were higher in all contusion-performed rats than those in the control (p<0.05). Compared with the other drugs, only APR significantly improved the haemorrhage/oedema scores compared to sham animals (p=0.024). CONCLUSIONS: Our findings demonstrate that moderate bilateral PC induced by blunt chest trauma leads to an early inflammatory process which is clearly associated with activation of the oxidant-antioxidant cascade. On this basis, early supportive treatment with DXM, NAC and APR may yield favourable results on pulmonary pathophysiological parameters which are adversely affected due to PC.