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1.
ChemSusChem ; 17(8): e202301418, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38189582

RESUMO

Waste PCBs the core of e-waste is rich in copper, tin, zinc, iron, and nickel. Leaching base metals from PCB used to be done in toxic, corrosive acidic/alkali mediums. In this work, an environmentally friendly method for leaching metals from thermally treated PCBs (TPCBs) of mobile phones was proposed using choline chloride based deep eutectic solvents (DES). DES selectivity and solubility of metals from metal oxides were the main screening criteria. FA-ChCl had the maximum solubility of Cu, Fe, and Ni, while Urea-ChCl had high Zn selectivity and solubility. Oxalic acid has high selectivity for Sn. FA-ChCl extracted Cu and Fe best at 16 h, 100 °C, and 1/30 g/mL. Urea-ChCl extracted Zn (90.4±2.9 %) from TPCBs at 100 °C, 21 h, 1/20 g/mL, and 400 rpm. Oxalic acid (1 M) removed 92.3±2.1 % Sn from TPCBs in 1 h at 80 °C and 1/20 g/mL. The shrinking core model-based kinetic investigation of FA-ChCl for Cu extraction showed a diffusion-controlled process. The proposed method is greener than mineral acids utilized for metal extraction.

2.
Nicotine Tob Res ; 26(4): 494-502, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-37837438

RESUMO

OBJECTIVES: Real-world evidence on exposure to harmful and potentially harmful constituents (HPHCs) and on biological effects in cigarette smokers who switch to electronic nicotine delivery systems (ENDS) can inform the health effects of switching. AIMS AND METHODS: This cross-sectional, observational study assessed adults who had smoked ≥10 cigarettes/day for ≥10 years, comparing 124 continuing cigarette smokers (Smokers) to 140 former smokers who switched to JUUL-brand ENDS exclusively for ≥6 months (Switchers). Assessments included biomarkers of exposure (BOEs) to select HPHCs, biomarkers of potential harm (BOPHs) related to smoking-related diseases, psychometric assessments of dependence on cigarettes and ENDS, respectively, and respiratory symptoms. Planned analyses compared geometric means, adjusted for demographic covariates; further analyses adjusted for additional lifestyle and smoking history covariates. RESULTS: Nicotine levels were significantly higher in Switchers (median time switched = 3 years), who were unusually heavy users of JUUL. All other BOEs, including NNAL and HPMA3 (primary endpoints), were significantly lower in Switchers than Smokers. Most BOPHs (sICAM-1 [primary], and eg, white blood cell count, MCP1, HbA1c) were significantly lower in Switchers than Smokers; HDL was significantly higher. Switchers reported significantly lower dependence on JUUL than Smokers did on cigarettes, and respiratory symptom scores were significantly lower among Switchers than Smokers. CONCLUSIONS: Compared to continuing smokers, smokers who switched to JUUL had substantially lower exposures to multiple HPHCs, favorable differences in markers of inflammation, endothelial function, oxidative stress, and cardiovascular risk, and fewer respiratory symptoms. These findings suggest that switching from cigarettes to JUUL likely reduces smokers' health risks. IMPLICATIONS: Short-term confinement studies and randomized clinical trials demonstrate that adult smokers who switch completely to ENDS experience substantial reductions in exposure to many smoking-related toxicants. This study extends those findings to longer periods of switching to JUUL-brand ENDS (almost 3 years on average) under naturalistic use conditions in real-world settings and also found that switching to JUUL resulted in favorable differences in BOPHs more proximally related to smoking-induced disease, as well as in respiratory symptoms. Smokers who switch to ENDS reduce their exposure to toxicants, likely reducing their disease risk.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Adulto , Humanos , Fumantes , Estudos Transversais , Fumar/efeitos adversos , Nicotina/efeitos adversos , Biomarcadores/análise , Substâncias Perigosas/análise
3.
J Environ Manage ; 335: 117581, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-36867901

RESUMO

The rapid increase in electronic waste (e-waste) generation and its unsustainable management pose a threat to the environment and human well-being. However, various valuable metals are present in e-waste, which makes it a potential secondary source to recover metals. Therefore, in the present study, efforts were made to recover valuable metals (Cu, Zn, and Ni) from waste printed circuit boards (WPCB) of computers using methanesulfonic acid (MSA). MSA is contemplated as a biodegradable green solvent and has a high solubility for various metals. The effect of various process parameters (MSA concentration, H2O2 concentration, stirring speed, liquid to solid ratio, time, and temperature) was investigated on metal extraction to optimize the process. At the optimized process conditions, 100% extraction of Cu and Zn was achieved, while Ni extraction was around 90%. The kinetic study for metal extraction was performed using a shrinking core model and findings showed that MSA-aided metal extraction is a diffusion-controlled process. Activation energies were found to be 9.35, 10.89, and 18.86 kJ/mol for Cu, Zn, and Ni extraction, respectively. Furthermore, the individual recovery of Cu and Zn was achieved using the combination of cementation and electrowinning, which resulted in 99.9% purity of Cu and Zn. The current study proposes a sustainable solution for the selective recovery of Cu and Zn from WPCB.


Assuntos
Resíduo Eletrônico , Peróxido de Hidrogênio , Humanos , Metais , Mesilatos , Reciclagem/métodos , Cobre
4.
Clin Case Rep ; 10(9): e6345, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36172332

RESUMO

Calcification of the intraocular lens is an uncommon phenomenon that usually follows an uncomplicated surgery. Here, the authors report the first case of a 66-year-old male patient who presented with defective vision and was diagnosed with sunflower pattern calcific deposits and Elschnig pearl pattern posterior capsular opacification in the right eye.

5.
N Z Med J ; 135(1548): 19-30, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-35728127

RESUMO

AIM: This study describes the developmental process of a series of anatomy games for medical students and analyses student participation and experiences around the gamification process. METHODS: Three diverse anatomy games were developed on the undergraduate medical curriculum. Based on students' playing and simultaneous learning experiences in each game, subsequent game contents were constructively modified. Students from three different universities participated in the study (total cohort=646); their experiences on the different games were documented and compared with each other. RESULTS: Feedback from 219 players showed that the games were fun (95%) and interesting (81%) and assisted their anatomy learning (97%); students' fun, interest and learning improved significantly in the two subsequent games (p<0.001). CONCLUSION: Carefully designed anatomy games create a fun-filled and interesting learning environment for undergraduate medical students. Learning experiences improved when students' feedback was appropriately addressed to constructively modify the subsequent learning resources.


Assuntos
Anatomia , Educação de Graduação em Medicina , Gamificação , Anatomia/educação , Currículo , Humanos , Aprendizagem , Nova Zelândia , Estudantes de Medicina
6.
Waste Manag ; 145: 29-37, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35500319

RESUMO

The heterogeneous nature of e-waste, which is a rich source of metals, polymers, glass fibres and ceramics, is troublesome. Multi-step processes are employed to effectively treat e-waste with minimum environmental impact. In this research, a subcritical to supercritical methanol environment was investigated to pre-treat e-waste, recovering non-metallic fractions and eventually concentrate metals from e-waste. Experiments were conducted in the temperature range of 150 °C to 300 °C at an autogenous pressure with initial atmospheric pressure. The mechanism of depolymerization was investigated by varying reaction time from 30 min to 240 min; solid to liquid ratio of 1:10 to 1:30 g/ml in a batch reactor under N2 environment. Comparative analysis of liquid products obtained after Supercritical Methanol (SCM) treatment for both Waste Random Access Memory (WRAM) and Waste Printed Circuit Board (WPCB) was done with pyrolyzed oil/liquid product. This research briefly illustrates oil and solid product compositional changes with operating temperature, pressure, and solid/liquid ratio range. The metal concentrations of copper, nickel, silver, zinc, and gold are greater than 90% after SCM treatment. For comparison, the feed material was pyrolyzed under the same condition, the difference in oil and solid products are assessed. In the end section, the environmental and economic benefits of SCM were also discussed compared to other supercritical and conventional technologies. An efficient and greener approach of supercritical solvent is proposed via this research for e-waste recycling.


Assuntos
Resíduo Eletrônico , Cobre/análise , Resíduo Eletrônico/análise , Metanol , Reciclagem , Prata/análise
7.
J Clin Diagn Res ; 11(6): CC17-CC20, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28764152

RESUMO

INTRODUCTION: Maximal oxygen consumption (VO2max) is an important measure of cardiorespiratory capacity of an individual at a given degree of fitness and oxygen availability. Risk of cardiovascular diseases increases with increasing degree of obesity and a low level of VO2max has been established as an independent risk factor for cardiovascular mortality. AIM: To determine VO2max in young adults and to find its correlation with Body Mass Index (BMI), Body Fat% and Fat Free Mass (FFM). MATERIALS AND METHODS: Fifty four (male=30, female=24) healthy young adults of age group18-25 years after screening by Physical Activity Readiness Questionnaire (PAR-Q) participated in the study. Height was measured by stadiometer. Weight was measured by digital weighing scale with 0.1 kg sensitivity. Body fat% was measured by Bioelectrical Impedance Analysis (BIA) method. FFM was calculated by subtracting fat mass from the body weight. VO2max (mL.kg-1.min-1) was obtained by Submaximal Exercise Test (SET) by first two stages of Bruce Protocol with the basis of linear relationship between Heart Rate (HR) and oxygen consumption (VO2). Data were analysed statistically in GraphPad Prism software version 6.01 for windows. RESULTS: VO2max (mL.kg-1.min-1) of male (43.25±7.25) was significantly (p<0.001) higher than female (31.65±2.10). BMI showed weak negative correlation (r= -0.3232, p=0.0171) with VO2max but Body Fat% showed strong negative correlation (r= -0.7505, p<0.001) with VO2max. FFM positively correlated (r=0.3727, p=0.0055) with VO2max. CONCLUSION: Increased body fat is associated with decreased level of VO2max in young adults. Obesity in terms of Fat% is a better parameter than BMI for prediction of low VO2max.

8.
Anat Cell Biol ; 50(2): 159-161, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28713621

RESUMO

It is quite common to see abnormal peritoneal folds in the abdominal cavity. Some of them might compress or strangulate the viscera and others might determine the direction of the flow of peritoneal fluid, pus or blood. Many unusual clinically important peritoneal folds such as Ladd's band, cysto-gastro-colic fold, omento-cystic fold, and cysto-colic fold have been reported earlier. Knowledge of these folds is important for radiologists, gastroenterologists, and surgeons. We report an unusual cysto-duodeno-colic fold observed during our dissection classes. The fold was seen to compress the duodenum and colon. The fold extended from the descending part of the duodenum and the transverse colon to the gallbladder. It enclosed the entire gallbladder. A case similar to this has not been reported yet. It is important for the gastroenterologists and laparoscopic surgeons to be aware of this fold to avoid misdiagnosis and iatrogenic injuries.

9.
Surg Radiol Anat ; 39(8): 931-933, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28124075

RESUMO

During our dissection classes, we saw a venous collar formed around the superior mesenteric artery (SMA) by the jejunal tributaries of superior mesenteric vein in an adult male cadaver. The jejunal tributaries united themselves to form two common jejunal veins. Upper common jejunal vein crossed superficial to SMA and opened into the SMV in front of the uncinate process of pancreas. The inferior common jejunal vein crossed behind the SMA from left to right and opened into the SMV, 4 cm below this level. A communicating vein connected the two common jejunal veins with each other.


Assuntos
Artéria Mesentérica Superior/anormalidades , Veias Mesentéricas/anormalidades , Anatomia/educação , Dissecação , Humanos
10.
J Clin Diagn Res ; 10(9): JC10-JC12, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27790469

RESUMO

INTRODUCTION: Creativity is a combination of ones' capacity to think outside the box, the gained knowledge and the passion for creating something. It very easily and effectively provides the creator a chance to be responsible for his/her creation and acts as a confidence booster for him/her. Creativity is inherent, but needs to be polished and nurtured. If nurtured well through proper motivation, the creator excels leaps and bounds. It develops an empathetic behaviour in the creator, when he allows his creations to be used by others. AIM: The study was done to generate learning resources through academically good students and make them available for the entire class. MATERIALS AND METHODS: Academically, top 16 students were involved in a project of their choice. The projects included preparation of question answers, powerpoint presentations, cross-word puzzles, videos, models, atlases and wall hangers etc., ten weeks were given to finish the project. The project was guided and monitored by teachers. The end product of the project was given to the entire class for use. The perception of users of the end products of the projects was recorded through mini interviews. RESULTS: All the students who took part in the project liked working on the project. They felt motivated, rewarded and had mastery on the topic which they used in the project. The students who did not do the project but used the end product of the project also liked the project work. They felt that the end products of the projects were simple, informative and creative. CONCLUSION: By participating in Student Project in Anatomy (SPA), the students get to show their total potential through these creative ways. It provides a fresh and welcome change from the common routine followed otherwise in medical schools. The outcome of the projects can help the entire class. This type of projects can be easily tailored into existing curriculum and in disciplines other than anatomy too.

11.
Biochem Mol Biol Educ ; 44(3): 241-5, 2016 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-26625860

RESUMO

Use of audio visual tools to aid in medical education is ever on a rise. Our study intends to find the efficacy of a video prepared on "fatty liver," a topic that is often a challenge for pre-clinical teachers, in enhancing cognitive processing and ultimately learning. We prepared a video presentation of 11:36 min, incorporating various concepts of the topic, while keeping in view Mayer's and Ellaway guidelines for multimedia presentation. A pre-post test study on subject knowledge was conducted for 100 students with the video shown as intervention. A retrospective pre study was conducted as a survey which inquired about students understanding of the key concepts of the topic and a feedback on our video was taken. Students performed significantly better in the post test (mean score 8.52 vs. 5.45 in pre-test), positively responded in the retrospective pre-test and gave a positive feedback for our video presentation. Well-designed multimedia tools can aid in cognitive processing and enhance working memory capacity as shown in our study. In times when "smart" device penetration is high, information and communication tools in medical education, which can act as essential aid and not as replacement for traditional curriculums, can be beneficial to the students. © 2015 by The International Union of Biochemistry and Molecular Biology, 44:241-245, 2016.


Assuntos
Recursos Audiovisuais , Educação de Graduação em Medicina , Avaliação Educacional/normas , Fígado Gorduroso/fisiopatologia , Aprendizagem , Estudantes de Medicina/psicologia , Ensino , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Multimídia , Estudos Retrospectivos
12.
Anat Sci Int ; 90(4): 324-6, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25022810

RESUMO

Knowledge of development and various possible positions of the appendix is important in understanding the pathophysiology of appendicitis. In the present case, we report on a lateral pouch type of appendix in a formalin-embalmed male cadaver. The appendix was found to be situated in a space between the caecum and the lateral abdominal wall. A short band of peritoneum extended from the right iliac fossa to the base of the appendix. The terminal part of the ileum was retroperitoneal and it was vertically situated in the right iliac fossa. Both the ileocaecal junction and the base of the appendix were located at the posterolateral wall of the caecum. The mesoappendix was unusual in position, and it extended from the appendix to the anterolateral wall of the caecum and commencement of the ascending colon. Documentation of rare anatomical variants of the appendix may hold significant clinical importance in diagnosis as well as surgical treatment of appendicitis.


Assuntos
Variação Anatômica , Apêndice/anatomia & histologia , Íleo/anatomia & histologia , Espaço Retroperitoneal/anatomia & histologia , Adulto , Ceco/anatomia & histologia , Colo Ascendente/anatomia & histologia , Humanos , Masculino
13.
JOP ; 15(6): 609-10, 2014 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-25435580

RESUMO

CONTEXT: Knowledge of variations of the vessels closely related to the pancreas adds greatly to the success of pancreatic surgery. Splenic vein is one of the vessels that are closely related to the pancreas. Its variations might not only change the haemodynamics in the vein but also cause unexpected bleeding during pancreatic surgery. CASE REPORT: During our dissection classes, we noted the variations in the course and termination of the splenic vein. After emerging from the spleen, it coursed upward and to the right, embedded in a groove on the anterior surface of body of pancreas. After reaching the upper border, it turned downwards and entered the body of the pancreas. After having a downward course in the body of pancreas, it emerged out and united with the superior mesenteric vein at an angle of about 160 degrees to form the portal vein. CONCLUSION: This peculiar course of the vein might predispose it for thrombosis in case of pancreatitis. It can also lead to iatrogenic injuries during pancreatic or splenic surgeries.

14.
Anat Sci Int ; 89(2): 118-21, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23959929

RESUMO

Knowledge about the variations of the sciatic nerve (SN) is important for many medical science disciplines. Its compression, entrapment or injury of any kind can result in loss of sensation, pain or motor disabilities in the lower limbs. We observed concurrent neurovascular variations in the gluteal region of an adult female cadaver. The SN had three roots as it emerged out of the greater sciatic foramen. The upper root passed above the piriformis; the middle and lower roots passed below the piriformis. The three roots joined to form the SN in the gluteal region. The inferior gluteal artery (IGA) was large, and it passed below the piriformis, between the middle and lower root of the SN. After a tortuous course, this artery continued down as the sciatic/ischiadic artery. The ischiadic artery (IA) was large in size and pierced the SN in the thigh. After piercing the nerve, it terminated by dividing into muscular branches. The inferior gluteal nerve emerged out from the pelvis through the greater sciatic foramen, above the level of the piriformis. The SN in this case was highly predisposed to compression by the piriformis, IGA or IA, which in turn may lead to altered cutaneous sensation or weakness of the muscles.


Assuntos
Nervo Isquiático/anatomia & histologia , Idoso , Variação Anatômica , Nádegas/irrigação sanguínea , Nádegas/inervação , Feminino , Humanos
15.
Int. j. morphol ; 31(3): 819-821, set. 2013. ilus
Artigo em Inglês | LILACS | ID: lil-694961

RESUMO

Femoral artery is the major artery of the lower limb. It shows some variations in its branching pattern. One of the rare but clinically important variations is the origin of deep circumflex iliac and inferior epigastric arteries from it instead of from external iliac artery. We report here the origin of inferior epigastric and deep circumflex iliac arteries from the femoral artery bilaterally. Both the arteries passed up deep to the inguinal ligament and had a normal course and distribution after crossing the inguinal ligament. Knowledge of these variations is of importance in plastic surgery, anterior approach to the hip joint, draining psoas abscess or reducing a femoral hernia.


La arteria femoral es la principal arteria del miembro inferior. Se observan algunas variaciones en su patrón de ramificación. Una variante rara, pero clínicamente importante es el origen común de las arterias circunfleja iliaca profunda y epigástrica inferior no desde la arteria ilíaca externa. Presentamos el origen bilateral de las arterias epigástricas inferiores y circunfleja ilíaca profunda desde la arteria femoral. Ambas arterias pasaron profundas al ligamento inguinal y tuvieron un curso y distribución normal después de cruzar el ligamento inguinal. El conocimiento de estas variaciones son de importancia en la cirugía plástica, en el acceso anterior a la articulación de la cadera, el drenaje absceso del músculo psoas mayor o para reducir una hernia femoral.


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Artéria Femoral/anormalidades , Artéria Ilíaca/anormalidades , Artérias Epigástricas/anormalidades , Coxa da Perna/irrigação sanguínea , Variação Anatômica , Cadáver , Dissecação
16.
Anat Cell Biol ; 46(1): 82-4, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23560240

RESUMO

A peculiar liver was found in an adult male cadaver during a dissection class for undergraduate medical students. The quadrate lobe and fissure for the ligamentum teres were totally absent. Thus, the cystic notch on the inferior border was very broad and deep, and the fundus and body of the gall bladder popped out through this notch. The cystic duct terminated into the right hepatic duct at the porta hepatis instead of terminating into the common hepatic duct. Awareness of variations of the lobes and fissures may minimize a misdiagnosis of liver problems. The aim of the current study was to alert radiologists and surgeons about possible variations in the external appearance and anomalies of the lobes and fissures of the liver.

17.
Anat Cell Biol ; 46(4): 296-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24386603

RESUMO

The subhepatic position of the cecum and appendix is a result of embryological reasons. Subhepatic appendicitis can cause diagnostic dilemmas. During the dissection of an adult male cadaver aged approximately 70 years, the subhepatic position of the cecum and appendix was noted. The appendix made a "U"-shaped bend and its tip was located in the paracolic position. The cecum had appendices epiploicae, and the terminal part of the ileum was retroperitoneal and had ascended vertically to the cecum from the right iliac fossa. Functionally, the sessile part of the ileum might restrict its peristaltic movements. The abnormal position of the terminal ileum might be mistaken for an ascending colon during laparoscopic surgery. The subhepatic position of the cecum and appendix might cause confusion in the diagnosis of acute appendicitis because the tenderness in such cases is not located at the McBurney's point.

18.
Oman Med J ; 26(6): e027, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28861181

RESUMO

Variation in the origin of long flexor tendons in the anterior compartment of forearm is common. During routine cadaveric dissection at Melaka Manipal Medical College (Manipal Campus), we observed a separate muscle belly and tendon of flexor digitorum superficialis (FDS) to the fifth digit in the right upper limb of a 60 year-old male cadaver. The anomalous muscle belly originated from the common flexor tendon from the medial epicondyle of the humerus and continued as a thin tendon at the middle of the forearm to get inserted into the middle phalanx of the fifth digit. This can be considered as a case of split flexor digitorum superficialis. Such muscle variations and knowledge of their frequency, appearance, and location can be helpful for surgeons.

19.
Rom J Morphol Embryol ; 51(3): 521-6, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20809030

RESUMO

Lateral obliquity of the forearm from the arm when the forearm is supinated and extended is called carrying angle. In this study carrying angle was measured using radiographs of adult individuals and morphometry was done on dry bones taking part in formation of human elbow (on lower end of humerus-trochlear angle and inclination angle of olecranon fossa, on upper end of ulna-olecranon-coronoid angle and length and width of inferior medial trochlear notch). On radiographs, the difference between male and female carrying angle and difference between carrying angle of right and left limbs (in both sexes together as well as in same sex) was statistically not significant. All the morphometric parameters measured in this study did not show any significant sexual dimorphism or difference between right and left side except the inclination angle of olecranon fossa, which was significantly more on right side. Different findings of carrying angle as reported by various authors could be due to racial difference or due to different methods used to measure carrying angle. Morphometric parameters were similar to findings of radiographic method of measuring carrying angle. These factors should also be considered in construction of elbow prosthesis as well as use of carrying angle in identification of skeletal remains.


Assuntos
Osso e Ossos/diagnóstico por imagem , Cotovelo/diagnóstico por imagem , Adulto , Feminino , Humanos , Úmero/diagnóstico por imagem , Masculino , Radiografia , Ulna/diagnóstico por imagem
20.
Proc Natl Acad Sci U S A ; 103(13): 5191-6, 2006 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-16551742

RESUMO

Carbon monoxide (CO), an endogenous cytoprotective product of heme oxygenase type-1 regulates target thrombotic and inflammatory genes in ischemic stress. Regulation of the gene encoding early growth response 1 (Egr-1), a potent transcriptional activator of deleterious thrombotic and inflammatory cascades, may govern CO-mediated ischemic lung protection. The exact signaling mechanisms underlying CO-mediated cytoprotection are not well understood. In this study we tested the hypothesis that inhibition of mitogen-activated protein kinase-dependent Egr-1 expression may be pivotal in CO-mediated ischemic protection. In an in vivo isogeneic rat lung ischemic injury model, inhaled CO not only diminished fibrin accumulation and leukostasis and improved gas exchange and survival but also suppressed extracellular signal-regulated kinase (ERK) activation, Egr-1 expression, and Erg DNA-binding activity in lung tissue. Additionally, CO-mediated inhibition of Egr-1 reduced expression of target genes, such as tissue factor, serpine-1, interleukin-1, and TNF-alpha. However, CO failed to inhibit serpine-1 expression after unilateral lung ischemia in mice null for the Egr-1 gene. In RAW macrophages in vitro, hypoxia-induced Egr-1 mRNA expression was ERK-dependent, and CO-mediated suppression of ERK activation resulted in Egr-1 inhibition. Furthermore, CO suppression of ERK phosphorylation was reversed by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one but was insensitive to cAMP-dependent protein kinase A inhibition with H89 and NO synthase inhibition with l-nitroarginine methyl ester. This finding indicates that CO suppresses ERK in a cGMP-dependent but cAMP/protein kinase A- and NO-independent manner. Together, these data identify a unifying molecular mechanism by which CO interrupts proinflammatory and prothrombotic mediators of ischemic injury.


Assuntos
Monóxido de Carbono/farmacologia , Proteína 1 de Resposta de Crescimento Precoce/genética , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Isquemia/metabolismo , Pneumopatias/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Animais , Linhagem Celular , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Proteína 1 de Resposta de Crescimento Precoce/deficiência , Sobrevivência de Enxerto , Hipóxia/induzido quimicamente , Hipóxia/genética , Hipóxia/metabolismo , Hipóxia/patologia , Isquemia/induzido quimicamente , Isquemia/genética , Isquemia/patologia , Pneumopatias/induzido quimicamente , Pneumopatias/genética , Pneumopatias/patologia , Transplante de Pulmão , Masculino , Camundongos , Camundongos Knockout , Óxido Nítrico/metabolismo , Ratos
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