Intervencije za lečenje primarne bilijarne ciroze: Kohranova analiza sistematskih pregleda sa meta-analizama i sekvencijalnim analizama randomizovanih kliničkih studija

Primary biliary cirrhosis is a chronic autoimmune-mediated liver disease characterised by progressive destruction of intrahepatic bile ducts, resulting in chronic cholestasis, portal inflammation, and fibrosis that can lead to cirrhosis and, ultimately, liver failure and the need for liver transplantation. The disease primarely affects middle‐aged women and is associated with osteoporosis ‐ either postmenopausal or secondary to the liver disease. Low bone mass is an important cause of morbidity in patients with primary biliary cirrhosis, leading to an increased risk of fractures, pain, and deformity. Treatment of primary biliary cirrhosis and osteoporosis associated with primary biliary cirrhosis is complicated. A number of drugs have been evaluated for patients with primary biliary cirrhosis (glucocorticosteroids, methotrexat, azathioprine, colchicine, cyclosporin, D-penicillamine, and chlorambucil). Ursodeoxycholic acid is the only drug approved for primary biliary cirrhosis by the U.S. Food and Drug Administration. Bezafibrate may be effective for treatment of primary biliary cirrhosis. Bisphosphonates and hormone replacement may be effective treatment options for osteoporosis in primary biliary cirrhosis, but the effects have only had limited assessment in systematic reviews. Therefore, interventions based on evidence are highly warranted. Cochrane reviews with meta-analyses and trial sequential analyses of randomised clinical trials generally provide the best available evidence for health care interventions and clinical practice. Such Cochrane reviews are used to assess and summarise benefits and harms of clinical interventions. Furthermore, Cochrane reviews will also reveal lack of evidence, and define the specific need for future randomised clinical trials. Objectives To summarize the evidence from Cochrane systematic reviews on treatment options for patients with primary biliary cirrhosis and osteoporosis associated with primary biliary cirrhosis...Primarna bilijarna ciroza je hronična autoimuna bolest jetre koju karakteriše progresivna destrukcija intrahepatičnih žučnih puteva sa posledičnom holestazom, portnom inflamacijom, i fibrozom što dovodi do nastanka ciroze jetre, i hepatičke insuficijencije sa transplantacijom jetre kao jedinom uspešnom terapijskom metodom. Više od 90% bolesnika su žene, prosečne starosti oko 50 godina. Najvažnija komplikacija bolesti vezana za holestazu je osteoporoza gde smanjenje koštane gustine dovodi do velikog rizika za nastanak preloma kostiju, bola i deformiteta. Lečenje primarne bilijarne ciroze, kao i osteoporoze u sklopu primarne bilijarne ciroze je veoma komplikovano. Za sada nema zadovoljavajuće specifične medicinske terapije koja se preporučuje za lečenje ove bolesti. Evaluirani su mnogi lekovi u terapiji ove bolesti (kortikosteroidi, metrotreksat, azatioprin, kolhicin, ciklosporin, D-penicilamin, i hlorambucil), ali do sada prikazani trajali su uglavnom bili kratki, mali i slabo kontrolisani. Ursodeoksiholna kiselina jedini je lek odobren za terapiju primarne bilijarne ciroze. U nekim kontrolisanim studijama konstatovano je da bezafibrat ima višestruka pozitivna dejstva kod bolesnika sa primarnom bilijarnom cirozom. Za bisfosfonate i supstitucionu hormonsku terapiju se očekuje da budu efikasni u terapiji osteoporoze u sklopu primarne bilijarne ciroze, ali ne postoje za sada dokazi efikasnoti u sistematskim pregledima. Kohranovi sistematski pregledi sa meta-analizama i sekvencijalnim analizama randomizovanih kliničkih studija sintetišu dokaze u cilju dobijanja pouzdanog, validnog i kompletnog pregleda proverenih dokaza o korisnim i štetnim efektima terapijskih procedura koristeći metodologiju u kojoj nema pristrasnosti u tumačenju rezultata i izvođenju zaključaka. Takođe, oni mogu ukazati na nedostatak dokaza i potrebu za budućim dobro dizajniranim randomizovanim kliničkim studijama..

Role of serotonin in development of esophageal and gastric fundal varices

AIM: To determine the effect of free serotonin concentrations in plasma on development of esophageal and gastric fundal varices. METHODS: This prospective study included 33 patients with liver cirrhosis and 24 healthy controls. Ultrasonography and measurement of serotonin concentration in plasma were carried out in both groups of subjects. The upper fiber panendoscopy was performed only in patients with liver cirrhosis. RESULTS: The mean plasma free serotonin levels were much higher in liver cirrhosis patients than in healthy controls (219.0 +/- 24.2 nmol/L vs 65.4 +/- 18.7 nmol/L, P lt 0.0001). There was no significant correlation be-tween serotonin concentration in plasma and the size of the esophageal varices according to Spearman coefficient of correlation (r(s) = -0.217, P > 0.05). However, the correlation of plasma serotonin concentration and gastric fundal varices was highly significant (r(s) = -0.601, P lt 0.01). CONCLUSION: Free serotonin is significant in pathogenesis of portal hypertension especially in development of fundal varices, indicating the clinical value of serotonergic receptor blockers in these patients

Unusual flexibility of mesophase pitch-derived carbon materials:an approach to the synthesis of graphene

Structural flexibility in a petroleum pitch-derived carbon material has been indirectly evaluated using X-ray diffraction (XRD), immersion calorimetry and inelastic neutron scattering (INS) measurements. Exposure of the carbon material to an organic solvent (e.g., n-nonane) gives rise to a large internal rearrangement, associated with a drastic re-ordering of the graphitic microdomains. These structural changes are also associated with a high flexibility of the internal porous network, as observed by inelastic neutron scattering measurements. The internal rearrangement and the structural flexibility could be responsible for the excellent performance of this kind of activated carbons in a wide variety of adsorption processes. Last but not least, the structural characteristics of these carbon materials composed of graphitic microdomains has been used to synthesize graphene “egg-like” flakes following a simple procedure based on exfoliation with organic solvents

Water in Deep Eutectic Solvents: New Insights From Inelastic Neutron Scattering Spectroscopy

The effect of water on the physicochemical properties of deep eutectic solvents (DES) is a trending research topic. In this work, inelastic neutron scattering (INS) spectroscopy, was used to probe intermolecular interactions in the water-deep eutectic solvent mixtures for the cases of choline chloride (the hydrogen bond acceptor) and three different hydrogen bond donors, with different degrees of acidity: urea, glycerol and lactic acid. It was found that quenching samples in liquid nitrogen is a procedure that may retain the liquid phase morphology of DES at the low temperatures required by INS spectroscopy. The three studied systems share the preference of water molecules to bind to chloride anion, as predicted by numerous molecular dynamics simulations. Despite this similarity, the three systems present several distinct INS features upon water addition that are related to their unique properties and structure at the molecular level. In the choline chloride:urea system, water molecules promote a strengthening of hydrogen bonds with the NH and OH donors, while for the choline chloride:lactic acid system INS probed the existence of solvated DES clusters instead of specifically interfering water molecules. This study takes advantage from the unique capabilities of INS and paves the way for future studies in these systems.publishe

Observation of Binding and Rotation of Methane and Hydrogen within a Functional Metal-Organic Framework

The key requirement for a portable store of natural gas is to maximize the amount of gas within the smallest possible space. The packing of methane (CH₄) in a given storage medium at the highest possible density is, therefore, a highly desirable but challenging target. We report a microporous hydroxyl-decorated material, MFM-300­(In) (MFM = Manchester Framework Material, replacing the NOTT designation), which displays a high volumetric uptake of 202 v/v at 298 K and 35 bar for CH₄ and 488 v/v at 77 K and 20 bar for H₂. Direct observation and quantification of the location, binding, and rotational modes of adsorbed CH₄ and H₂ molecules within this host have been achieved, using neutron diffraction and inelastic neutron scattering experiments, coupled with density functional theory (DFT) modeling. These complementary techniques reveal a very efficient packing of H₂ and CH₄ molecules within MFM-300­(In), reminiscent of the condensed gas in pure component crystalline solids. We also report here, for the first time, the experimental observation of a direct binding interaction between adsorbed CH₄ molecules and the hydroxyl groups within the pore of a material. This is different from the arrangement found in CH₄/water clathrates, the CH₄ store of nature

Unusual flexibility of mesophase pitch-derived carbon materials:an approach to the synthesis of graphene

Structural flexibility in a petroleum pitch-derived carbon material has been indirectly evaluated using X-ray diffraction (XRD), immersion calorimetry and inelastic neutron scattering (INS) measurements. Exposure of the carbon material to an organic solvent (e.g., n-nonane) gives rise to a large internal rearrangement, associated with a drastic re-ordering of the graphitic microdomains. These structural changes are also associated with a high flexibility of the internal porous network, as observed by inelastic neutron scattering measurements. The internal rearrangement and the structural flexibility could be responsible for the excellent performance of this kind of activated carbons in a wide variety of adsorption processes. Last but not least, the structural characteristics of these carbon materials composed of graphitic microdomains has been used to synthesize graphene “egg-like” flakes following a simple procedure based on exfoliation with organic solvents

Common variable immunodeficiency complicated with hemolytic uremic syndrome

Common variable immunodeficiency is a primary immunodeficiency disease characterized by reduced serum immunoglobulins and heterogeneous clinical features. Recurrent pyogenic infections of upper and lower respiratory tracts are the main clinical manifestations of common variable immunodeficiency. Hemolytic uremic syndrome is a multisystemic disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ ischemia due to platelet aggregation in the arterial microvasculature. This is one of the rare cases of patients diagnosed with common variable immunodeficiency, which was complicated by hemolytic uremic syndrome

Host–guest selectivity in a series of isoreticular metal–organic frameworks: observation of acetylene-to-alkyne and carbon dioxide-to-amide interactions

In order to develop new porous materials for applications in gas separations such as natural gas upgrading, landfill gas processing and acetylene purification it is vital to gain understanding of host-substrate interactions at a molecular level. Herein we report a series of six isoreticular metal-organic frameworks (MOFs) for selective gas adsorption. These materials do not incorporate open metal sites and thus provide an excellent platform to investigate the effect of the incorporation of ligand functionality via amide and alkyne groups on substrate binding. By reducing the linker length of our previously reported MFM-136, we report much improved CO2/CH4 (50:50) and CO2/N2 (15:85) selectivity values of 20.2 and 65.4, respectively (1 bar and 273 K), in the new amide-decorated MOF, MFM-126. The CO2 separation performance of MFM-126 has been confirmed by dynamic breakthrough experiments. In situ inelastic neutron scattering and synchrotron FT-IR microspectroscopy were employed to elucidate dynamic interactions of adsorbed CO2 molecules within MFM-126. Upon changing the functionality to an alkyne group in MFM-127, the CO2 uptake decreases but the C2H2 uptake increases by 68%, leading to excellent C2H2/CO2 and C2H2/CH4 selectivities of 3.7 and 21.2, respectively. Neutron powder diffraction enabled the direct observation of the preferred binding domains in MFM-126 and MFM-127, and, to the best of our knowledge, we report the first example of acetylene binding to an alkyne moiety in a porous material, with over 50% of the acetylene observed within MFM-127 displaying interactions (less than 4 Å) with the alkyne functionality of the framework

Intervencije za lečenje primarne bilijarne ciroze: Kohranova analiza sistematskih pregleda sa meta-analizama i sekvencijalnim analizama randomizovanih kliničkih studija

Primary biliary cirrhosis is a chronic autoimmune-mediated liver disease characterised by progressive destruction of intrahepatic bile ducts, resulting in chronic cholestasis, portal inflammation, and fibrosis that can lead to cirrhosis and, ultimately, liver failure and the need for liver transplantation. The disease primarely affects middle‐aged women and is associated with osteoporosis ‐ either postmenopausal or secondary to the liver disease. Low bone mass is an important cause of morbidity in patients with primary biliary cirrhosis, leading to an increased risk of fractures, pain, and deformity. Treatment of primary biliary cirrhosis and osteoporosis associated with primary biliary cirrhosis is complicated. A number of drugs have been evaluated for patients with primary biliary cirrhosis (glucocorticosteroids, methotrexat, azathioprine, colchicine, cyclosporin, D-penicillamine, and chlorambucil). Ursodeoxycholic acid is the only drug approved for primary biliary cirrhosis by the U.S. Food and Drug Administration. Bezafibrate may be effective for treatment of primary biliary cirrhosis. Bisphosphonates and hormone replacement may be effective treatment options for osteoporosis in primary biliary cirrhosis, but the effects have only had limited assessment in systematic reviews. Therefore, interventions based on evidence are highly warranted. Cochrane reviews with meta-analyses and trial sequential analyses of randomised clinical trials generally provide the best available evidence for health care interventions and clinical practice. Such Cochrane reviews are used to assess and summarise benefits and harms of clinical interventions. Furthermore, Cochrane reviews will also reveal lack of evidence, and define the specific need for future randomised clinical trials. Objectives To summarize the evidence from Cochrane systematic reviews on treatment options for patients with primary biliary cirrhosis and osteoporosis associated with primary biliary cirrhosis...Primarna bilijarna ciroza je hronična autoimuna bolest jetre koju karakteriše progresivna destrukcija intrahepatičnih žučnih puteva sa posledičnom holestazom, portnom inflamacijom, i fibrozom što dovodi do nastanka ciroze jetre, i hepatičke insuficijencije sa transplantacijom jetre kao jedinom uspešnom terapijskom metodom. Više od 90% bolesnika su žene, prosečne starosti oko 50 godina. Najvažnija komplikacija bolesti vezana za holestazu je osteoporoza gde smanjenje koštane gustine dovodi do velikog rizika za nastanak preloma kostiju, bola i deformiteta. Lečenje primarne bilijarne ciroze, kao i osteoporoze u sklopu primarne bilijarne ciroze je veoma komplikovano. Za sada nema zadovoljavajuće specifične medicinske terapije koja se preporučuje za lečenje ove bolesti. Evaluirani su mnogi lekovi u terapiji ove bolesti (kortikosteroidi, metrotreksat, azatioprin, kolhicin, ciklosporin, D-penicilamin, i hlorambucil), ali do sada prikazani trajali su uglavnom bili kratki, mali i slabo kontrolisani. Ursodeoksiholna kiselina jedini je lek odobren za terapiju primarne bilijarne ciroze. U nekim kontrolisanim studijama konstatovano je da bezafibrat ima višestruka pozitivna dejstva kod bolesnika sa primarnom bilijarnom cirozom. Za bisfosfonate i supstitucionu hormonsku terapiju se očekuje da budu efikasni u terapiji osteoporoze u sklopu primarne bilijarne ciroze, ali ne postoje za sada dokazi efikasnoti u sistematskim pregledima. Kohranovi sistematski pregledi sa meta-analizama i sekvencijalnim analizama randomizovanih kliničkih studija sintetišu dokaze u cilju dobijanja pouzdanog, validnog i kompletnog pregleda proverenih dokaza o korisnim i štetnim efektima terapijskih procedura koristeći metodologiju u kojoj nema pristrasnosti u tumačenju rezultata i izvođenju zaključaka. Takođe, oni mogu ukazati na nedostatak dokaza i potrebu za budućim dobro dizajniranim randomizovanim kliničkim studijama..