169 research outputs found
Redox phospholipidomics of enzymatically generated oxygenated phospholipids as specific signals of programmed cell death
High fidelity and effective adaptive changes of the cell and tissue metabolism to changing environments require strict coordination of numerous biological processes. Multicellular organisms developed sophisticated signaling systems of monitoring and responding to these different contexts. Among these systems, oxygenated lipids play a significant role realized via a variety of re-programming mechanisms. Some of them are enacted as a part of pro-survival pathways that eliminate harmful or unnecessary molecules or organelles by a variety of degradation/hydrolytic reactions or specialized autophageal processes. When these βpartialβ intracellular measures are insufficient, the programs of cells death are triggered with the aim to remove irreparably damaged members of the multicellular community. These regulated cell death mechanisms are believed to heavily rely on signaling by a highly diversified group of molecules, oxygenated phospholipids (PLox). Out of thousands of detectable individual PLox species, redox phospholipidomics deciphered several specific molecules that seem to be diagnostic of specialized death programs. Oxygenated cardiolipins (CLs) and phosphatidylethanolamines (PEs) have been identified as predictive biomarkers of apoptosis and ferroptosis, respectively. This has led to decoding of the enzymatic mechanisms of their formation involving mitochondrial oxidation of CLs by cytochrome c and endoplasmic reticulum-associated oxidation of PE by lipoxygenases. Understanding of the specific biochemical radical-mediated mechanisms of these oxidative reactions opens new avenues for the design and search of highly specific regulators of cell death programs. This review emphasizes the usefulness of such selective lipid peroxidation mechanisms in contrast to the concept of random poorly controlled free radical reactions as instruments of non-specific damage of cells and their membranes. Detailed analysis of two specific examples of phospholipid oxidative signaling in apoptosis and ferroptosis along with their molecular mechanisms and roles in reprogramming has been presented
ΠΠ»ΠΈΡΠ½ΠΈΠ΅ Π±ΠΈΠΎΠ³Π΅Π½Π½ΡΡ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ² Π½Π° ΡΠΈΡΠΎΡΠΊΡΡΡΠ°ΠΊΡΠΈΡ ΠΊΠ°Π΄ΠΌΠΈΡ ΠΈΠ· Π·Π°Π³ΡΡΠ·Π½Π΅Π½Π½ΠΎΠΉ ΠΏΠΎΡΠ²Ρ
The influence of substances containing biogenic elements (potassium chloride, sodium phosphate, ammonium nitrate, potassium and urea nitrate) on phytoextraction degree of cadmium from soil by cultivated oat (Avena sativa L.), cutting lettuce (Lactuca sativa L.) and charlock (Sinapis arvensis L.) has been investigated. As the results of experiment the factors used for estimation of relationship between the environment and a physiological role of a chemical element, and also for revealing of its share in biotic turnover and of a role of organisms-indicators and organisms-concentrators have been calculated: phytotoxic effect and factor of biological absorbing of cadmium by plants. It is shown that potassium nitrate promote the extraction of cadmium from soil in a greater degree in comparison with other substances containing biogenic elements.ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΎ Π²Π»ΠΈΡΠ½ΠΈΠ΅ Π²Π΅ΡΠ΅ΡΡΠ² , ΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΡ
Π±ΠΈΠΎΠ³Π΅Π½Π½ΡΠ΅ ΡΠ»Π΅ΠΌΠ΅Π½ΡΡ ( Ρ
Π»ΠΎΡΠΈΠ΄Π° ΠΊΠ°Π»ΠΈΡ , ΡΠΎΡΡΠ°ΡΠ° Π½Π°ΡΡΠΈΡ , Π½ΠΈΡΡΠ°ΡΠ° Π°ΠΌΠΌΠΎΠ½ΠΈΡ , Π½ΠΈΡΡΠ°ΡΠ° ΠΊΠ°Π»ΠΈΡ ΠΈ ΠΌΠΎΡΠ΅Π²ΠΈΠ½Ρ ) Π½Π° ΡΡΠ΅ΠΏΠ΅Π½Ρ ΡΠΈΡΠΎΡΠΊΡΡΡΠ°ΠΊΡΠΈΠΈ ΠΊΠ°Π΄ΠΌΠΈΡ ΠΈΠ· ΠΏΠΎΡΠ²Ρ ΠΎΠ²ΡΠΎΠΌ ΠΏΠΎΡΠ΅Π²Π½ΡΠΌ (Avena sativa L.), ΡΠ°Π»Π°ΡΠΎΠΌ Π»ΠΈΡΡΠΎΠ²ΡΠΌ (Lactuca sativa L.) ΠΈ Π³ΠΎΡΡΠΈΡΠ΅ΠΉ ΠΏΠΎΠ»Π΅Π²ΠΎΠΉ (Sinapis arvensis L.). ΠΠΎ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ°ΠΌ ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ° ΡΠ°ΡΡΡΠΈΡΠ°Π½Ρ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»ΠΈ, ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΡΡΠΈΠ΅ΡΡ Π΄Π»Ρ ΠΎΡΠ΅Π½ΠΊΠΈ ΡΠ²ΡΠ·ΠΈ ΡΡΠ΅Π΄Ρ ΠΈ ΡΠΈΠ·ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠΎΠ»ΠΈ Ρ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠ°, Π° ΡΠ°ΠΊΠΆΠ΅ Π΄Π»Ρ Π²ΡΡΠ²Π»Π΅Π½ΠΈΡ Π΅Π³ΠΎ ΡΡΠ°ΡΡΠΈΡ Π² Π±ΠΈΠΎΡΠΈΡΠ΅ΡΠΊΠΎΠΌ ΠΊΡΡΠ³ΠΎΠ²ΠΎΡΠΎΡΠ΅, ΡΠΎΠ»ΠΈ ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌΠΎΠ²-ΠΈΠ½Π΄ΠΈΠΊΠ°ΡΠΎΡΠΎΠ² ΠΈ ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌΠΎΠ²-ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΎΡΠΎΠ²: ΡΠΈΡΠΎΡΠΎΠΊΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΡΡΡΠ΅ΠΊΡ ΠΈ ΠΊΠΎΡΡΡΠΈΡΠΈΠ΅Π½Ρ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΏΠΎΠ³Π»ΠΎΡΠ΅Π½ΠΈΡ ΠΊΠ°Π΄ΠΌΠΈΡ ΡΠ°ΡΡΠ΅Π½ΠΈΡΠΌΠΈ. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ Π½ΠΈΡΡΠ°Ρ ΠΊΠ°Π»ΠΈΡ Π² Π±ΠΎΠ»ΡΡΠ΅ΠΉ ΡΡΠ΅ΠΏΠ΅Π½ΠΈ, ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ Π΄ΡΡΠ³ΠΈΠΌΠΈ Π²Π΅ΡΠ΅ΡΡΠ²Π°ΠΌΠΈ, ΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΠΌΠΈ Π±ΠΈΠΎΠ³Π΅Π½Π½ΡΠ΅ ΡΠ»Π΅ΠΌΠ΅Π½ΡΡ, ΡΠΏΠΎΡΠΎΠ±ΡΡΠ²ΡΠ΅Ρ ΠΈΠ·Π²Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΊΠ°Π΄ΠΌΠΈΡ ΠΈΠ· ΠΏΠΎΡΠ²Ρ
ΠΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΡΠ½ΡΠ°ΡΠ½ΠΎΠΉ ΠΊΠΈΡΠ»ΠΎΡΡ Π² ΠΏΡΠΎΡΠ΅ΡΡΠ΅ ΡΠΈΡΠΎΡΠΊΡΡΡΠ°ΠΊΡΠΈΠΈ ΡΠ²ΠΈΠ½ΡΠ° ΠΈ ΠΊΠ°Π΄ΠΌΠΈΡ ΠΈΠ· Π·Π°Π³ΡΡΠ·Π½Π΅Π½Π½ΡΡ ΠΏΠΎΡΠ²
Succinic acid influence on migration properties of lead and cadmium in soil-plant system has been investigated. It has been shown that the addition the activator (succinic acid) into soil increases the efficiency of phytoextraction of lead and cadmium. The optimum conditions of succinic acid usage as the process activator have been established.Π ΡΠ°Π±ΠΎΡΠ΅ ΠΈΠ·ΡΡΠ΅Π½ΠΎ Π²Π»ΠΈΡΠ½ΠΈΠ΅ ΡΠ½ΡΠ°ΡΠ½ΠΎΠΉ ΠΊΠΈΡΠ»ΠΎΡΡ Π½Π° ΠΌΠΈΠ³ΡΠ°ΡΠΈΠΎΠ½Π½ΡΠ΅ ΡΠ²ΠΎΠΉΡΡΠ²Π° ΡΠ²ΠΈΠ½ΡΠ° ΠΈ ΠΊΠ°Π΄ΠΌΠΈΡ Π² ΡΠΈΡΡΠ΅ΠΌΠ΅ Β«ΠΏΠΎΡΠ²Π°-ΡΡΡΠ΅Π½ΠΈΡΒ». Π£ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ Π²Π½Π΅ΡΠ΅Π½ΠΈΠ΅ Π² ΠΏΠΎΡΠ²Ρ Π°ΠΊΡΠΈΠ²Π°ΡΠΎΡΠ° - ΡΠ½ΡΠ°ΡΠ½ΠΎΠΉ ΠΊΠΈΡΠ»ΠΎΡΡ ΠΏΠΎΠ²ΡΡΠ°Π΅Ρ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΏΡΠΎΡΠ΅ΡΡΠ° ΡΠΈΡΠΎΡΠΊΡΡΡΠ°ΠΊΡΠΈΠΈ ΡΠ²ΠΈΠ½ΡΠ° ΠΈ ΠΊΠ°Π΄ΠΌΠΈΡ. Π£ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½Ρ ΠΎΠΏΡΠΈΠΌΠ°Π»ΡΠ½ΡΠ΅ ΡΡΠ»ΠΎΠ²ΠΈΡ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ ΡΠ½ΡΠ°ΡΠ½ΠΎΠΉ ΠΊΠΈΡΠ»ΠΎΡΡ Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ Π°ΠΊΡΠΈΠ²Π°ΡΠΎΡΠ° ΠΏΡΠΎΡΠ΅ΡΡΠ°
The influence of salinity on the effects of Multi-walled carbon nanotubes on polychaetes
Salinity shifts in estuarine and coastal areas are becoming a topic of concern and are one of the main factors influencing nanoparticles behaviour in the environment. For this reason, the impacts of multiwalled carbon nanotubes (MWCNTs) under different seawater salinity conditions were evaluated on the common ragworm Hediste diversicolor, a polychaete species widely used as bioindicator of estuarine environmental quality. An innovative method to assess the presence of MWCNT aggregates in the sediments was used for the first time. Biomarkers approach was used to evaluate the metabolic capacity, oxidative status and neurotoxicity of polychaetes after long-term exposure. The results revealed an alteration of energy-related responses in contaminated polychaetes under both salinity conditions, resulting in an increase of metabolism and expenditure of their energy reserves (lower glycogen and protein contents). Moreover, a concentration-dependent toxicity (higher lipid peroxidation, lower ratio between reduced and oxidized glutathione and activation of antioxidant defences and biotransformation mechanisms) was observed in H. diversicolor, especially when exposed to low salinity. Additionally, neurotoxicity was observed by inhibition of Cholinesterases activity in organisms exposed to MWCNTs at both salinities.publishe
Π‘ΡΡΠ°ΡΠ΅Π³ΠΈΡ DOTS β ΠΏΡΡΡ ΠΊ ΡΡΠΊΠΎΡΠ΅Π½Π½ΠΎΠΌΡ ΠΈΠ·Π»Π΅ΡΠ΅Π½ΠΈΡ Π²ΠΏΠ΅ΡΠ²ΡΠ΅ Π²ΡΡΠ²Π»Π΅Π½Π½ΡΡ Π±ΠΎΠ»ΡΠ½ΡΡ Π»Π΅Π³ΠΎΡΠ½ΡΠΌ ΡΡΠ±Π΅ΡΠΊΡΠ»Π΅Π·ΠΎΠΌ Π² Π ΠΎΡΡΠΈΠΈ
DOTS strategy includes several important points, primarily, detection of tuberculosis patients and a strong monitoring of treatment efficacy.Specialists on lung tuberculosis from Tomsk have 5-year experience in work with DOTS programme. They observed 675 patients asked medical care in tuberculosis settings of Tomsk region from the March 1995 to November 1996. The patients ere divided into the group A and B. The group A received anti-tuberculosis therapy adopted in Russia. The group Π was given directly observed treatment short course (DOTS) according to WHO standard. It included the intensive phase (2 months for new diagnosed cases and 3 months for repeated therapy course) and the continued phase of 2β4 (new diagnosed cases) to 5 months (repeated course) length. Typical WHO modes were used the first line drugs, such as isoniasid, rifampicin, pyrasinamid, etambutol, streptomycin. The therapy delayed results were assessed with criteria accepted by WHO and in Russia as well. Seventy one per cent of the patients recovered: 69% from the group A and 74% from the group B. The treatment failures were registered in 15 (4.2%) patients of the group A and 18 (5.6%) of the group B. Residual lesions of respiratory system were less severe in the group A patients just at the early period; there was no significant difference between the groups by the 30-th month of the observation. Meantime the cost-effectiveness of WHO standard treatment is 1.9 times less than that of Russian traditional schemes. Generally, a positive tendency in lung tuberculosis patientsβ treatment and observation effectiveness has been noted in the Tomsk region for the last 5 years due to the DOTS strategy, so that it takes a positive role for tuberculosis patientsβ cure.Π‘ΡΡΠ°ΡΠ΅Π³ΠΈΡ DOTS Π²ΠΊΠ»ΡΡΠ°Π΅Ρ ΡΡΠ΄ Π²Π°ΠΆΠ½ΡΡ
ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ², Π² ΠΏΠ΅ΡΠ²ΡΡ ΠΎΡΠ΅ΡΠ΅Π΄Ρ Π²ΡΡΠ²Π»Π΅Π½ΠΈΠ΅ Π±ΠΎΠ»ΡΠ½ΡΡ
ΡΡΠ±Π΅ΡΠΊΡΠ»Π΅Π·ΠΎΠΌ β Π±Π°ΡΠΈΠ»Π»ΠΎΠ²ΡΠ΄Π΅Π»ΠΈΡΠ΅Π»Π΅ΠΉ ΠΈ ΡΡΡΠΎΠ³ΠΈΠΉ ΠΌΠΎΠ½ΠΈΡΠΎΡΠΈΠ½Π³ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π»Π΅ΡΠ΅Π½ΠΈΡ Π±ΠΎΠ»ΡΠ½ΠΎΠ³ΠΎ.Π’ΠΎΠΌΡΠΊΠΈΠ΅ ΡΡΠΈΠ·ΠΈΠ°ΡΡΡ ΠΈΠΌΠ΅ΡΡ 5-Π»Π΅ΡΠ½ΠΈΠΉ ΠΎΠΏΡΡ ΡΠ°Π±ΠΎΡΡ ΠΏΠΎ ΠΏΡΠΎΠ³ΡΠ°ΠΌΠΌΠ΅ DOTS. ΠΠ°Π±Π»ΡΠ΄Π°Π»ΠΎΡΡ 675 Π±ΠΎΠ»ΡΠ½ΡΡ
, ΠΎΠ±ΡΠ°ΡΠΈΠ²ΡΠΈΡ
ΡΡ Π² ΠΏΡΠΎΡΠΈΠ²ΠΎΡΡΠ±Π΅ΡΠΊΡΠ»Π΅Π·Π½ΡΠ΅ ΡΡΡΠ΅ΠΆΠ΄Π΅Π½ΠΈΡ Π’ΠΎΠΌΡΠΊΠΎΠΉ ΠΎΠ±Π»Π°ΡΡΠΈ Π² ΠΏΠ΅ΡΠΈΠΎΠ΄ Ρ ΠΌΠ°ΡΡΠ° 1995 Π³. ΠΏΠΎ Π½ΠΎΡΠ±ΡΡ 1996 Π³. ΠΠ°ΡΠΈΠ΅Π½ΡΡ Π±ΡΠ»ΠΈ ΡΠ°Π·Π΄Π΅Π»Π΅Π½Ρ Π½Π° Π³ΡΡΠΏΠΏΡ Π ΠΈ Π: Π³ΡΡΠΏΠΏΠ° Π ΠΏΠΎΠ»ΡΡΠ°Π»Π° Π»Π΅ΡΠ΅Π½ΠΈΠ΅ ΠΏΠΎ ΠΏΡΠΈΠ½ΡΠΈΠΏΠ°ΠΌ ΡΡΠ°Π΄ΠΈΡΠΈΠΎΠ½Π½ΠΎΠΉ ΡΠΎΡΡΠΈΠΉΡΠΊΠΎΠΉ ΡΡΠΈΠ·ΠΈΠ°ΡΡΠΈΠΈ, Π³ΡΡΠΏΠΏΠ΅ Π Π½Π°Π·Π½Π°ΡΠ°Π»ΠΈ ΠΊΡΠ°ΡΠΊΠΎΡΡΠΎΡΠ½ΡΠΉ ΠΊΡΡΡ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΏΠΎΠ΄ Π½Π΅ΠΏΠΎΡΡΠ΅Π΄ΡΡΠ²Π΅Π½Π½ΡΠΌ Π½Π°Π±Π»ΡΠ΄Π΅Π½ΠΈΠ΅ΠΌ (ΠΠΠ₯) ΠΏΠΎ ΡΡΠ°Π½Π΄Π°ΡΡΠ°ΠΌ ΠΠΠ, ΡΠΎΡΡΠΎΡΡΠΈΠΉ ΠΈΠ· ΠΈΠ½ΡΠ΅Π½ΡΠΈΠ²Π½ΠΎΠΉ ΡΠ°Π·Ρ (2 ΠΌΠ΅Ρ Π΄Π»Ρ Π½ΠΎΠ²ΡΡ
ΡΠ»ΡΡΠ°Π΅Π² ΠΈ 3 ΠΌΠ΅Ρ Π΄Π»Ρ ΠΏΠΎΠ²ΡΠΎΡΠ½ΠΎΠ³ΠΎ Π»Π΅ΡΠ΅Π½ΠΈΡ) ΠΈ ΠΏΡΠΎΠ΄ΠΎΠ»ΠΆΠ°ΡΡΠ΅ΠΉ ΡΠ°Π·Ρ Π΄Π»ΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΡΡ ΠΎΡ 2β4 ΠΌΠ΅Ρ (Π½ΠΎΠ²ΡΠ΅ ΡΠ»ΡΡΠ°ΠΈ) Π΄ΠΎ 5 ΠΌΠ΅Ρ (ΠΏΠΎΠ²ΡΠΎΡΠ½ΠΎΠ΅ Π»Π΅ΡΠ΅Π½ΠΈΠ΅). ΠΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π»ΠΈΡΡ ΠΊΠ»Π°ΡΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠ΅ΠΆΠΈΠΌΡ ΠΠΠ Ρ Π½Π°Π·Π½Π°ΡΠ΅Π½ΠΈΠ΅ΠΌ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² ΠΏΠ΅ΡΠ²ΠΎΠΉ Π»ΠΈΠ½ΠΈΠΈ: ΠΈΠ·ΠΎΠ½ΠΈΠ°Π·ΠΈΠ΄, ΡΠΈΡΠ°ΠΌΠΏΠΈΡΠΈΠ½, ΠΏΠΈΡΠ°Π·ΠΈΠ½Π°ΠΌΠΈΠ΄, ΡΡΠ°ΠΌΠ±ΡΡΠΎΠ», ΡΡΡΠ΅ΠΏΡΠΎΠΌΠΈΡΠΈΠ½. ΠΡΠ΄Π°Π»Π΅Π½Π½ΡΠ΅ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΎΡΠ΅Π½ΠΈΠ²Π°Π»ΠΈΡΡ ΠΏΠΎ ΠΊΡΠΈΡΠ΅ΡΠΈΡΠΌ, ΠΏΡΠΈΠ½ΡΡΡΠΌ ΠΊΠ°ΠΊ ΠΠΠ, ΡΠ°ΠΊ ΠΈ Π² ΡΠΎΡΡΠΈΠΉΡΠΊΠΎΠΉ ΡΡΠΈΠ·ΠΈΠ°ΡΡΠΈΠΈ. ΠΠ·Π»Π΅ΡΠ΅Π½ΠΎ 71% ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ²: Π² Π³ΡΡΠΏΠΏΠ΅ Π β 69%, Π² Π³ΡΡΠΏΠΏΠ΅ Π β 74%. ΠΠ΅ΡΠ΄ΠΎΠ²Π»Π΅ΡΠ²ΠΎΡΠΈΡΠ΅Π»ΡΠ½ΡΠ΅ ΠΈΡΠΎΠ³ΠΈ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΊΠΎΠ½ΡΡΠ°ΡΠΈΡΠΎΠ²Π°Π½Ρ Π² Π³ΡΡΠΏΠΏΠ΅ Π Ρ 15 (4,2%) ΡΠ΅Π»ΠΎΠ²Π΅ΠΊ, Π² Π³ΡΡΠΏΠΏΠ΅ Π β Ρ 18 (5,6%) Π±ΠΎΠ»ΡΠ½ΡΡ
. Π₯Π°ΡΠ°ΠΊΡΠ΅Ρ ΠΎΡΡΠ°ΡΠΎΡΠ½ΡΡ
ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠΉ ΡΠΎ ΡΡΠΎΡΠΎΠ½Ρ ΠΎΡΠ³Π°Π½ΠΎΠ² Π΄ΡΡ
Π°Π½ΠΈΡ Π±ΡΠ» Π±ΠΎΠ»Π΅Π΅ Π±Π»Π°Π³ΠΎΠΏΡΠΈΡΡΠ½ΡΠΌ Π² Π³ΡΡΠΏΠΏΠ΅ Π ΡΠΎΠ»ΡΠΊΠΎ Π½Π° ΡΠ°Π½Π½Π΅ΠΌ ΡΡΠ°ΠΏΠ΅, Π° ΠΊ 30 ΠΌΠ΅Ρ Π½Π°Π±Π»ΡΠ΄Π΅Π½ΠΈΡ ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈ Π·Π½Π°ΡΠΈΠΌΠΎΠΉ ΡΠ°Π·Π½ΠΈΡΡ ΠΌΠ΅ΠΆΠ΄Ρ Π³ΡΡΠΏΠΏΠ°ΠΌΠΈ Π ΠΈ Π Π½Π΅ ΠΎΡΠΌΠ΅ΡΠ΅Π½ΠΎ. ΠΠΌΠ΅ΡΡΠ΅ Ρ ΡΠ΅ΠΌ Π·Π°ΡΡΠ°ΡΡ Π½Π° Π»Π΅ΡΠ΅Π½ΠΈΠ΅ ΠΏΠΎ ΠΏΡΠΎΡΠΎΠΊΠΎΠ»Π°ΠΌ ΠΠΠ Π² 1,9 ΡΠ°Π·Π° ΠΌΠ΅Π½ΡΡΠ΅, ΡΠ΅ΠΌ ΠΏΠΎ ΠΏΡΠΈΠ½ΡΡΡΠΌ Π² Π ΠΎΡΡΠΈΠΈ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠ°ΠΌ. Π ΡΠ΅Π»ΠΎΠΌ Π±Π»Π°Π³ΠΎΠ΄Π°ΡΡ ΡΡΡΠ°ΡΠ΅Π³ΠΈΠΈ DOTS Π² Π’ΠΎΠΌΡΠΊΠΎΠΉ ΠΎΠ±Π»Π°ΡΡΠΈ Π·Π° ΠΏΠΎΡΠ»Π΅Π΄Π½ΠΈΠ΅ 5 Π»Π΅Ρ Π΄ΠΎΡΡΠΈΠ³Π½ΡΡΠ° ΠΏΠΎΠ»ΠΎΠΆΠΈΡΠ΅Π»ΡΠ½Π°Ρ Π΄ΠΈΠ½Π°ΠΌΠΈΠΊΠ° ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Π΅ΠΉ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΈ Π΄ΠΈΡΠΏΠ°Π½ΡΠ΅ΡΠ½ΠΎΠ³ΠΎ Π½Π°Π±Π»ΡΠ΄Π΅Π½ΠΈΡ Π±ΠΎΠ»ΡΠ½ΡΡ
ΡΡΠ±Π΅ΡΠΊΡΠ»Π΅Π·ΠΎΠΌ, ΡΡΠΎ ΠΏΠΎΠ΄ΡΠ²Π΅ΡΠΆΠ΄Π°Π΅Ρ ΠΏΠΎΠ·ΠΈΡΠΈΠ²Π½ΡΡ ΡΠΎΠ»Ρ ΡΡΡΠ°ΡΠ΅Π³ΠΈΠΈ Π² ΠΈΠ·Π»Π΅ΡΠ΅Π½ΠΈΠΈ Π±ΠΎΠ»ΡΠ½ΡΡ
Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study
Background: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8Β·0 years [IQR 4Β·2β11Β·4], 1191 [59Β·3%] male and 818 [40Β·7%] female, and 825 [41Β·1%] White). 680 (33Β·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34Β·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24Β·2%) with glucocorticoids alone; 59 (2Β·9%) patients received other combinations, including biologicals, and 85 (4Β·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1Β·09 (95% CI 0Β·75β1Β·58; corrected p value=1Β·00) for intravenous immunoglobulin plus glucocorticoids and 0Β·93 (0Β·58β1Β·47; corrected p value=1Β·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1Β·04 (95% CI 0Β·91β1Β·20; corrected p value=1Β·00) for intravenous immunoglobulin plus glucocorticoids, and 0Β·84 (0Β·70β1Β·00; corrected p value=0Β·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0Β·15 [95% CI 0Β·11β0Β·20]; p<0Β·0001) and glucocorticoids alone (0Β·68 [0Β·50β0Β·93]; p=0Β·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0Β·50 [95% CI 0Β·38β0Β·67]; p<0Β·0001) or glucocorticoids alone (0Β·63 [0Β·45β0Β·88]; p=0Β·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health
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