Enfisema pulmonar em deficientes de Alfa-1 Antitripsina

Enfisema pulmonar em deficientes de Alfa-1 Antitripsin

Влияние недостаточности α1-антитрипсина на поражение легких

Effects of alfa-1-antitripsin deficiency on lung disease.Влияние недостаточности α1-антитрипсина на поражение легких

Structural and functional analysis of alpha-1-antitrypsin gene in human lung diseases

Alfa-1-antitripsin je inhibitor serin proteaza čija je osnovna biološka funkcija inhibicija elastaze neutrofila – enzima koji učestvuje u degradaciji elastina i koji dovodi do oštećenja tkiva pluća. Deficijencija i disfunkcija alfa-1-antitripsina leže u osnovi više oboljenja od kojih su najčešći emfizem pluća i oboljenja jetre, a mogu predstavljati i faktor rizika za nastanak karcinoma pluća. Ovaj rad je imao za cilj da ispita postojanje strukturnih promena u kodirajućim egzonima gena za alfa-1-antitripsin kod ispitanika sa emfizemom pluća i kod ispitanika sa karcinomom pluća, kao i da istraži funkcionalne posledice otkrivenih promena i njihov eventualni značaj u nastanku i razvoju bolesti. Strukturnom analizom gena za alfa-1-antitripsin DGGE metodom i DNK sekvenciranjem detektovano je prisustvo deficijentnih varijanti Z, S i Mmalton, kao i dve nove varijante označene kao G320R i V321F. Elektroforezom u denaturišućem poliakrilamidnom gelu uočeno je da varijante G320R i V321F migriraju brže u odnosu na WT varijantu, a analizom u denaturišućem poliakrilamidnom gelu sa 5M ureom pokazano je da ove varijante verovatno imaju smanjenu hidrofobnost u odnosu na WT varijantu. Analizom formiranih kompleksa između alfa-1-antitripsina i elastaze pankreasa u SDS gelovima, utvrđeno je da se inhibitorna aktivnost ispitivanih varijanti ne razlikuje od inhibitorne aktivnosti WT varijante proteina. Nativna elektroforeza preparata alfa-1-antitripsina inkubiranih na različitim temperaturama pokazala je da mutirane varijante proteina imaju blago smanjenu termostabilnost u odnosu na WT protein, a elektroforeza proteina eksprimiranih u COS7 ćelijskoj liniji pokazala je da varijante G320R i V321F pod fiziološkim uslovima ne formiraju polimere. Metodom imunofluorescencije na tranzijentno transfekovanim COS7 ćelijama pokazano je da su varijante G320R i V321F, kao i WT protein, lokalizovane u Goldžijevom aparatu i da se ne zadržavaju u endoplazmatičnom retikulumu...Alpha-1-antitrypsin is a serine protease inhibitor whose main biological function is inhibition of neutrophil elastase – enzyme capable of digestion of elastin and involved in lung tissue destruction. Deficiency and disfunction of alpha-1-antitrypsin is associated with emphysema and liver disease, and can represent a risk factor for development of lung cancer. The objective of this work was to perform structural analysis of alpha-1-antitrypsin gene in subjects with emphysema and lung cancer, as well as to perform functional analysis of discovered variants in order to estimate their role in disease development. Structural analysis of alpha-1-antitrypsin gene, using DGGE and DNA sequencing, revealed presence of deficient variants Z, S and Mmalton, as well as two novel variants – G320R and V321F. Denaturing PAGE analysis showed that variants G320R and V321F exibited increased gel mobility compared to WT variant, and electrophoresis in the presence of 5M urea showed that these variants effected the protein structure, probably by changing its hydrophobicity. Nondenaturing electrophoresis of heat treated proteins showed that both variants had slightly decreased thermostability when compared to WT variant and non-denaturing PAGE of COS7 expressed proteins showed that these variants did not form polymers under physiological conditions. Inibitory activity of variants G320R and V321F, determined by analysis of SDS-PAGE resistant complexes between alpha-1-antitrypsin and porcine pancreas elastase, was same as in WT variant. Immunofluorescence of transiently transfected COS7 cell line showed that variants G320R and V321F, as well as WT protein, were predominantly localized at Golgi apparatus indicating that they are not retained in endoplasmic reticulum..

Hepatocellular Carcinoma: Risk Factors and Diagnosis

Hepatocellular carcinoma, also known as hepatocarcinoma, is the most frequent type of primary liver cancer and the world's second leading cause of death, with a mortality rate of 700.000 per year. Due to the difficulty in diagnosing hepatocarcinoma because there are no obvious symptoms, the survival rate of hepatocarcinoma patients is still very low, particularly in Southeast Asian countries. Hepatocarcinoma is still a major health issue in Indonesia, with a very low median survival rate. The number of risk factors that cause hepatocarcinoma is what causes differences in hepatocarcinoma incidence across countries. This literature review aims to determine risk factors and to confirm the diagnosis of hepatocarcinoma. This literature review was conducted using the keywords “Hepatocellular Carcinoma AND risk factors AND diagnosis” from PubMed, Google Scholar, and non-peer-reviewed literature. This article uses 16 articles that were used as references in its preparation. In conclusion, hepatitis B and C virus, liver cirrhosis, fatty liver disease, diabetes, alcohol use, aflatoxin exposure, aristolochic acid exposure, smoking, and HIV are risk factors for hepatocarcinoma. On all individuals with hepatocarcinoma risk factors, screening procedures with US and AFP were carried out. An abdominal CT scan or an MRI with contrast can both be used to provide a firm diagnosis of hepatocarcinoma. A liver biopsy is used to confirm the diagnosis of space-occupying lesions that lack typical imaging characteristics

Prevalence of S and Z alpha 1-antitrypsin mutations in patients with pancreatic diseases in Serbian population

Jedan od osnovnih izazova u proučavanju patologije bolesti pankreasa predstavlja dalje razjašnjavanje uloge proteaza i antiproteaza, zbog toga što poremećena ravnoteža između njih može dovesti do oštećenja pankreasa. Alfa 1-antitripsin (AAT) je jedan od najvažnijih inhibitora proteolitičkih enzima u serumu, među kojima su i enzimi pankreasa: tripsin, himotripsin i elastaza. Pretpostavlja se da mutacije u AAT genu mogu da utiču na pojavu i razvoj bolesti pankreasa. Prisustvo najčešćih mutacija u AAT genu, označenih kao Z i S, analizirano je u 160 pacijenata sa bolestima pankreasa (50 pacijenata sa kancerom pankreasa, 50 pacijenata sa hroničnim pankreatitisom i 60 pacijenata sa dijabetesom tipa 2) i u 129 zdravih osoba. Prisustvo mutacija detektovano je analizom dužina restrikcionih fragmenata. Jedan pacijent sa kancerom pankreasa je bio heterozigotni nosilac Z mutacije, kao i jedan pacijent sa dijabetesom tipa 2. Jedan pacijent sa hroničnim pankreatitisom je bio heterozigotni nosilac S mutacije. Dve najčešće mutacije u AAT genu su bile statistički značajno učestalije kod pacijenata sa bolestima pankreasa (3 / 160 pacijenata, alelska frekvencija 0,9%) nego u kontrolnoj grupi (1 / 129 osoba, alelska frekvencija 0,4%). Rezultati ove studije, koje ukazuju na moguću povezanost Z i S mutacija sa umerenim povećanjem rizika za razvoj bolesti pankreasa.One of the key points in research of pancreatic disease pathology is further elucidation of the role of proteases and antiproteases, since their imbalance can lead to pancreatic injury. Alpha 1-antitrypsin (AAT) is one of the most important serum inhibitors of proteolytic enzymes, including pancreatic enzymes trypsin, chymotrypsin and elastase. It is speculated that mutations in the AAT gene may influence the onset and the development of pancreatic disease. The presence of the most common AAT mutations Z and S was analyzed in 160 patients with pancreatic diseases (50 patients with pancreatic cancer, 50 patients with chronic pancreatitis and 60 patients with type 2 diabetes mellitus) and 129 healthy individuals by PCR-mediated site-directed mutagenesis (PSM) method. One patient with pancreatic cancer was found to be a carrier of Z mutation, as well as one patient with type 2 diabetes mellitus. One patient with chronic pancreatitis was found to be a carrier of S mutation. The common AAT mutations were statistically significantly over-represented in patients with pancreatic diseases (3 of 160 patients, allelic frequency 0.9%) than in the control group (1 of 129 individuals, allelic frequency 0.4%). The results of this study, requiring confirmation, suggest that common AAT mutations Z and S may be associated with a modest increase in susceptibility to the development of pancreatic disease

Роль эндотелиальной дисфункции в развитии нарушений микроциркуляции и легочно-сердечной гемодинамики у больных хронической обструктивной болезнью легких с различными фенотипами α1-антитрипсина

The aim of this study was to investigate structural and functional changes of pulmonary vessels and cardiopulmonary blood flow in COPD patients with different alpha-1-antitrypsin (A1AT) phenotypes and endothelial dysfunction. Methods. Patients with COPD stage 2 to 3 (n = 113) with different A1AT phenotypes underwent clinical and radiological examination; endothelial dysfunction markers were measured. Results. More severe COPD was associated with more severe pulmonary microcirculation disorders and more significant perfusion defects. Patients with ZZ phenotype had worse pulmonary blood flow abnormalities compared to patients with MM phenotype. Pulmonary blood flow abnormalities were closely related to endothelial dysfunction (r = 0.75) and were more significant than structural abnormalities diagnosed on multi spiral computed tomography. Severe disorders of pulmonary blood flow were not accompanied by severe pulmonary hypertension. Conclusions: Blood levels of main endothelial dysfunction markers were directly related to COPD severity. Angiotensin-converting enzyme concentration was significantly below the normal level and was related to pulmonary artery pressure. The pulmonary blood flow differed in patients with different A1AT phenotypes and COPD stage 3 or higher. Perfusion defects were more severe in patients with ZZ phenotype.Нарушению эндотелиальной функции сосудов малого круга кровообращения в развитии и прогрессировании хронической обструктивной болезни легких (ХОБЛ) в настоящее время уделяется особое внимание. Эндотелиоциты участвуют также в трансцитозе α1-антитрипсина (α1-АТ) из легочной микроциркуляции в эпителиальные клетки легких и альвеолы. Снижение концентрации α1-АТ в крови приводит к деструкции эластических волокон легких и развитию эмфиземы, т. к. α1-АТ является основным ингибитором эластаз, выделяемых альвеолярными макрофагами и полиморфноядерными лейкоцитами, обеспечивая 90 % антиэластазной активности. Однако данные о взаимосвязи эндотелиальной дисфункции (ЭД) с дисциркуляторными изменениями в легочном микрососудистом русле и состоянием легочно-сердечной гемодинамики у больных ХОБЛ с разными фенотипами α1-АТ практически отсутствуют. Цель. Оценка структурно-функциональных, сосудистых изменений в легких и состояния легочно-сердечной гемодинамики в зависимости от степени выраженности ЭД у больных ХОБЛ с разными фенотипами α1-АТ. Материалы и методы. Проанализированы результаты комплексного клинико-рентгенорадиологического исследования и показателей маркеров ЭД у пациентов (n = 113) с ХОБЛ II–III стадии с разными фенотипами α1-АТ. Результаты. По мере нарастания степени тяжести ХОБЛ увеличиваются нарушения микроциркуляции в легких, нарастает дефицит перфузии, причем у больных с патологическим ZZ-фенотипом изменения легочного кровотока были более значимыми, чем у пациентов c нормальным (ММ) фенотипом. Изменения кровообращения в легких коррелировали в высокой степени (r = 0,75) с ЭД. Нарушения легочной микроциркуляции всегда были более выраженными по сравнению со структурными изменениями, полученными при выполнении мультиспиральной компьютерной томографии. Значительное нарушение кровообращения в легких не сопровождалось столь же выраженным повышением давления в системе малого круга кровообращения. Заключение. По мере нарастания степени тяжести ХОБЛ уровень основных белков-маркеров ЭД увеличивается. Продемонстрировано достоверное снижение нормальных показателей ангиотензинпревращающего фермента в обеих группах и их зависимость от повышения давления в легочной артерии. Установлено, что изменения в легочном микрососудистом русле у больных ХОБЛ с разными фенотипами α1-АТ различаются, начиная с III стадии заболевания, а дефицит перфузии более выражен у больных с ZZ-фенотипом α1-АТ

Pola Resistensi Antibiotik pada Pasien Penyakit Paru Obstruktif Kronik Eksaserbasi Akut di RSUP Dr. M. Djamil Padang Periode 1 Januari 2013 - 31 Desember 2015

Peningkatan resistensi bakteri penyebab PPOK eksaserbasi akut terhadap antibiotik yang umum digunakan oleh klinisi dalam pemberian terapi empiris akan menurunkan efektivitas terapi PPOK eksaserbasi akut dan meningkatkan morbiditas dan mortalitas. Penelitian ini bertujuan untuk mengetahui pola resistensi antibiotik pada bakteri yang ditemukan pada kultur sputum pasien PPOK dan PPOK eksaserbasi akut di RSUP Dr. M. Djamil Padang periode 1 Januari 2013 – 31 Desember 2015. Metode penelitian yang digunakan adalah deskriptif dan data yang diperoleh diolah secara manual dan disajikan dalam tabel distribusi frekuensi. Data didapat dari rekam medis pasien dan data Laboratorium Mikrobiologi terkait hasil kultur sputum dan uji sensitivitas antibiotik pada pasien PPOK dan PPOK eksaserbasi akut di RSUP Dr. M. Djamil Padang periode 1 Januari 2013 – 31 Desember 2015. Dari penelitian terhadap data sekunder rekam medis, hasil uji sensitivitas antibiotik dan jenis bakteri dari 105 pasien, menunjukkan bahwa usia pasien PPOK terbanyak adalah diatas 65 tahun dan jenis kelamin pasien yang paling banyak mengalami PPOK adalah laki-laki. Tipe PPOK eksaserbasi akut yang paling umum ditemukan adalah PPOK eksaserbasi akut tipe 1. Bakteri yang paling banyak ditemukan adalah Klebsiella sp. sebanyak 51 temuan. Antibiotik yang paling sensitif terhadap bakteri yang ditemukan adalah Netilmisin, sedangkan antibiotik yang paling resisten adalah Ampisilin. Kata kunci : antibiotik, PPOK eksaserbasi akut, sensitivita

Neonatal Sludge: A finding of congenital hypothyroidism

Congenital hypothyroidism is one of the most urgent diseases of the neonate. When diagnosed and treated at an early stage, its most important complication, mental retardation, is preventable. The signs of congenital hypothyroidism are nonspecific in neonates. Only 5% of the cases have characteristic clinical findings. One of the most important and earliest signs is prolonged jaundice during the neonatal period. We report herein a case of congenital hypothyroidism, who presented with icterus accompanied with sludge formation into the gallbladder, which disappeared after treatment with L-thyroxine

HUBUNGAN FAKTOR RESIKO DENGAN KEJADIAN PADA PENYAKIT PARU OBSTRUKSI KRONIK DI PUSKESMAS MANDALA

The main cause of Chronic Obstructive Pulmonary Disease is smoking or exposure to secondhand smoke from active smokers or smoke inhalation in passive smokers. Other causes are air pollution, workplace exposure, and genetic factors. This type of research is analytical research with a cross sectional approach which aims to study the existence of a variable relationship dynamics. In this study, the sample was 30 patients from the Mandala Health Center. Generally, COPD sufferers are those aged 45 years to 65 years where 21 of the 30 people suffer from risk. The chi-square test results show that there is a relationship between risk factors and the incidence of COPD in the Tembung Mandala 2018 Health Center Working Area