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As controversy persists regarding the benefits of mechanical circulatory support in septic shock with a predominantly vasoplegic phenotype, preclinical studies may provide a useful alternative to fill the actual knowledge gap. Here, we investigated the physiologic responses to venoarterial extracorporeal membrane oxygenation therapy (VA-ECMO) in a clinically relevant porcine peritonitis-induced model of refractory vasodilatory septic shock. In 12 anesthetized, mechanically ventilated, and instrumented domestic pigs, septic shock was induced by intraperitoneally inoculating autologous feces. After reaching the threshold for refractory vasodilatory shock (norepinephrine dose ≥1 μg/kg/min), the pigs were randomized into the conservative treatment group (control) or the VA-ECMO group (target flow 100 mL/kg/min). The time to develop refractory vasodilatory shock was similar in both groups (18.8 h in the ECMO group, 18.1 h in the control group). There was no difference between the groups in terms of time to death measured from the point of reaching the predefined vasopressor threshold (7.1 h for the ECMO group, 7.9 h for the control group). The initiation of ECMO resulted in a markedly increased fluid and vasopressor support. Although treatment with ECMO compromised neither renal nor carotid blood flow initially, both progressively decreased later during the experiment. The pattern of sepsis-induced multiorgan injury, alterations in energy metabolism, and the systemic inflammatory response were remarkably similar between both groups. In conclusion, the application of VA-ECMO in this model of peritonitis-induced refractory vasodilatory septic shock aggravated hemodynamic deterioration. Our findings contribute to increasing equipoise with respect to the clinical utility of VA-ECMO in refractory vasodilatory shock.
Je mnoho dôkazov pre obavy, že pandémia chrípky skutočne hrozí a ak na ňu nebudú pediatri a verejné zdravotníctvo pripravené, bude znamenať katastrofu. Vírus chrípky A obsahuje 2 dôležité glykoproteíny hemaglutinín (H, 16 mutácií) a neuraminidáza (N, 9 mutácií), ktoré sú základom typizácie vírusu a ich mutácie sú príčinou menlivosti vírusu, úniku imunitným mechanizmom hostiteľa a opakovaných epidémií. Dokázalo sa, že vírus vtáčej chrípky A (H5N1) doteraz infikoval najmenej 344 osôb, z čoho zomrelo 211 chorých, postihnutie detí je časté. V liečbe chrípky sú t.č. najvhodnejšie inhibítory neuraminidázy oseltamivír a zanamivír, najlepšou prevenciou je očkovanie. Uvádzajú sa všeobecne uznávané indikácie a formy liečby a odporúčania pre očkovanie.
There is evidence of flu pandemics and if pediatricians and public health do not take particular safety precautions, the disaster will be inevitable. Virus of flu A consists of 2 important glycoproteins hemaglutinin (H, 16 mutations) and neuraminidase (N, 9 mutations) which are the basis for the virus classification and mutations are the cause of the virus mutability, resistance to immune mechanisms of the host and recurrent epidemics. At least 344 persons were reported to be infected by the virus H5N1, 211 of them died. Children affliction is common. Currently inhibitors of neuraminidase oseltamivir and zanamivir seem to the best flu therapy. The best prevention is inoculation. Generally recognized indications and therapeutical forms and guidelines for inoculation are presented in the article.
Pea seed-borne mosaic virus (PSbMV) significantly reduces yields in a broad spectra of legumes. The eukaryotic translation initiation factor has been shown to confer resistance to this pathogen, thus implying that translation and proteome dynamics play a role in resistance. This study presents the results of a proteome-wide analysis of Pisum sativum L. response to PSbMV infection. LC-MS profiling of two contrasting pea cultivars, resistant (B99) and susceptible (Raman) to PSbMV infection, detected >2300 proteins, 116 of which responded to PSbMV ten and/or twenty days post-inoculation. These differentially abundant proteins are involved in number of processes that have previously been reported in the plant-pathogen response, including protein and amino acid metabolism, stress signaling, redox homeostasis, carbohydrate metabolism, and lipid metabolism. We complemented our proteome-wide analysis work with targeted analyses of free amino acids and selected small molecules, fatty acid profiling, and enzyme activity assays. Data from these additional experiments support our findings and validate the biological relevance of the observed proteome changes. We found surprising similarities in the resistant and susceptible cultivars, which implies that a seemingly unaffected plant, with no detectable levels of PSbMV, actively suppresses viral replication. BIOLOGICAL SIGNIFICANCE: Plant resistance to PSbMV is connected to translation initiation factors, yet the processes involved are still poorly understood at the proteome level. To the best of our knowledge, this is the first survey of the global proteomic response to PSbMV in plants. The combination of label-free LC-MS profiling and two contrasting cultivars (resistant and susceptible) provided highly sensitive snapshots of protein abundance in response to PSbMV infection. PSbMV is a member of the largest family of plant viruses and our results are in accordance with previously characterized potyvirus-responsive proteomes. Hence, the results of this study can further extend our knowledge about these pathogens. We also show that even though no viral replication is detected in the PSbMV-resistant cultivar B99, it is still significantly affected by PSbMV inoculation.
- MeSH
- chromatografie kapalinová MeSH
- eukaryotické iniciační faktory MeSH
- hrách setý virologie MeSH
- interakce hostitele a patogenu * MeSH
- nemoci rostlin virologie MeSH
- odolnost vůči nemocem genetika MeSH
- Potyvirus patogenita MeSH
- proteomika metody MeSH
- rostlinné viry MeSH
- tandemová hmotnostní spektrometrie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BALB/c mice bearing syngeneic BCL1 leukemia, a mouse model of human chronic lymphocytic leukemia, were treated with polymer-bound doxorubicin conjugate targeted with BCL1-specific monoclonal antibody. Such treatment can cure up to 100% of mice and the cured mice show long-lasting resistance to BCL1 leukemia. We show that both CD4+ and CD8+ T cells are required for establishment of the resistance, but only CD8+ T cells are necessary for its maintenance. BCL1 cells express MHC class I and II and also costimulatory molecules CD80 and CD86, which can aid eliciting of antitumor response. On the other hand, BCL1 cells also use several immunoescape mechanisms, such as expression of PD-L1, PD-L2, and interleukin-10. BCL1 cells thus can be recognized by BCL1-specific T cells, but instead of effective priming, such T cells are anergized or deleted by apoptosis. Moreover, BCL1 leukemia progression is accompanied by robust expansion of CD4+CD25+Foxp3+ regulatory T (Treg) cells. Although it has been shown that depletion of Treg cells in tumor-bearing mice can retard tumor growth, direct evidence that expansion of Treg cells can promote tumor growth was lacking. In this study, we provide first direct evidence that expanded Treg cells can indeed promote tumor progression by using mice with selectively expanded Treg cells before inoculation of BCL1 leukemia. Finally, we have also shown that elimination of some immunoescape mechanism (e.g., deletion of Treg) can significantly improve the therapeutic outcome of chemotherapy.
- MeSH
- antibiotika antitumorózní farmakologie MeSH
- CD8-pozitivní T-lymfocyty imunologie MeSH
- doxorubicin analogy a deriváty farmakologie MeSH
- imunokonjugáty farmakologie imunologie MeSH
- kyseliny polymethakrylové farmakologie MeSH
- leukemie B-buněčná farmakoterapie imunologie MeSH
- monoklonální protilátky imunologie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- regulační T-lymfocyty imunologie MeSH
- únik nádoru z imunitní kontroly imunologie účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
Mineralization of native organic matter and U-14C-glucose was followed by measuring the formation of CO2 and its radioactivity in chernozem soil presterilized by gamma-radiation and inoculated with a washed suspension of Cellulomonas sp. cells. The introduced bacteria mineralized the soil organic component to a higher extent in variants enriched with glucose. This so-called priming effect of glucose was observed also in the presence of chloramphenicol, inhibiting the growth of the bacteria. The increased mineralization of the native soil organic fraction was also detected in samples that were not enriched with glucose when the bacterial suspension was first disintegrated ultrasonically and the material then used for the inoculation. Possible participation of phenomena of the type of cometabolism and activation of cell membrane transport mechanisms on the occurrence of the priming effect of glucose in the soil is discussed.
- MeSH
- Actinomycetales účinky léků růst a vývoj metabolismus MeSH
- chemická deprese MeSH
- chloramfenikol farmakologie MeSH
- glukosa farmakologie MeSH
- kultivační techniky MeSH
- oxid uhličitý biosyntéza MeSH
- průmyslová hnojiva MeSH
- půdní mikrobiologie * MeSH
- sterilizace MeSH
- záření gama MeSH
- Publikační typ
- časopisecké články MeSH
Piglets from 4 to 8 weeks of age originated from a Cryptosporidium-free research breed were orally inoculated with 1 × 10(6) infectious oocysts of Cryptosporidium scrofarum. The number of shed oocysts per gram of faeces served to describe the infection intensity and prepatent period. In addition, faecal samples collected daily and tissue samples of the small and large intestine collected at 30 days post-inoculation were examined for the C. scrofarum small subunit ribosomal RNA gene using PCR. The piglets inoculated at 4-weeks of age remained uninfected, whereas 5-week-old and older animals were fully susceptible with a prepatent period ranging from 4 to 8 days. Susceptible pigs shed oocysts intermittently, and shedding intensity, reaching a mean maximum of 6000 oocysts per gram, did not differ significantly among infected animals. This study demonstrates that pigs become susceptible to C. scrofarum infection as late as 5-weeks of age. The mechanisms of age related susceptibility remain unknown.
- MeSH
- Cryptosporidium genetika MeSH
- feces parazitologie MeSH
- geny rRNA genetika MeSH
- kryptosporidióza imunologie patologie veterinární MeSH
- nemoci prasat imunologie patologie MeSH
- počet parazitárních vajíček MeSH
- prasata MeSH
- věkové faktory MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Gas gangrene is a rare and potentially fatal surgical complication, most often associated with contaminated traumatic wounds or more rarely following cases of abdominal surgery. The following article describes a case of gas gangrene in the right lower limb of a 34-year-old patient following an elective posterior tibial tendon transfer. The surgery was performed in bloodless fashion, utilizing a surgical tourniquet. Fifteen months prior to the procedure, the patient was attacked by a wild boar, resulting in a tear of the upper calf with complete transection of the right common fibular nerve. The patient underwent a total of three acute surgical procedures, of which the third resulted in below knee amputation. The patient then underwent a final corrective procedure and was fitted with a suitable leg prosthesis. In the discussion, three possible pathophysiological mechanisms of gas gangrene development are described - iatrogenic inoculation of bacteria during injection of local anesthetics for conduction anesthesia, iatrogenic inoculation of bacteria during the posterior tibial tendon transfer and activation of latent clostridial spores within the original wound caused by the wild boar. We consider the third mechanism most likely, as boar tusks contaminated with soil and debris are a more likely source of clostridial spores, than sterile surgical instruments. Furthermore, it is likely the surgical tourniquet played a key role in activating latent spores within the patient wound, as changes in tissue oxygen levels are a common cause of spore activation. Thus, we suggest caution in utilizing bloodless operating fields in elective cases with a history of open contaminated wounds, as the iatrogenic hypoxia can potentially activate sporulent bacteria within the patient's wound.
- MeSH
- amputace MeSH
- dospělí MeSH
- elektivní chirurgické výkony MeSH
- gangréna plynatá * etiologie MeSH
- lidé MeSH
- nervus peroneus MeSH
- přenos šlachy metody MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Communities of arbuscular mycorrhizal fungi (AMF) are crucial for promoting plant productivity in most terrestrial systems, including anthropogenically managed ecosystems. Application of AMF inocula has therefore become a widespread practice. It is, however, pertinent to understand the mechanisms that govern AMF community composition and their performance in order to design successful manipulations. Here we assess whether the composition and plant growth-promotional effects of a synthetic AMF community can be altered by inoculum additions of the isolates forming the community. This was determined by following the effects of three AMF isolates, each inoculated in two propagule densities into a preestablished AMF community. Fungal abundance in roots and plant growth were evaluated in three sequential harvests. We found a transient positive response in AMF abundance to the intraspecific inoculation only in the competitively weakest isolate. The other two isolates responded negatively to intra- and interspecific inoculations, and in some cases plant growth was also reduced. Our results suggest that increasing the AMF density may lead to increased competition among fungi and a trade-off with their ability to promote plant productivity. This is a key ecological aspect to consider when introducing AMF into soils.
- MeSH
- DNA fungální chemie genetika MeSH
- houby klasifikace genetika růst a vývoj MeSH
- kořeny rostlin mikrobiologie MeSH
- molekulární sekvence - údaje MeSH
- mykorhiza klasifikace genetika růst a vývoj MeSH
- počet mikrobiálních kolonií MeSH
- sekvenční analýza DNA MeSH
- společenstvo * MeSH
- vývoj rostlin MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
High-throughput sequencing technologies were used to identify plant viruses in cereal samples surveyed from 2012 to 2017. Fifteen genome sequences of a tenuivirus infecting wheat, oats, and spelt in Estonia, Norway, and Sweden were identified and characterized by their distances to other tenuivirus sequences. Like most tenuiviruses, the genome of this tenuivirus contains four genomic segments. The isolates found from different countries shared at least 92% nucleotide sequence identity at the genome level. The planthopper Javesella pellucida was identified as a vector of the virus. Laboratory transmission tests using this vector indicated that wheat, oats, barley, rye, and triticale, but none of the tested pasture grass species (Alopecurus pratensis, Dactylis glomerata, Festuca rubra, Lolium multiflorum, Phleum pratense, and Poa pratensis), are susceptible. Taking into account the vector and host range data, the tenuivirus we have found most probably represents European wheat striate mosaic virus first identified about 60 years ago. Interestingly, whereas we were not able to infect any of the tested cereal species mechanically, Nicotiana benthamiana was infected via mechanical inoculation in laboratory conditions, displaying symptoms of yellow spots and vein clearing evolving into necrosis, eventually leading to plant death. Surprisingly, one of the virus genome segments (RNA2) encoding both a putative host systemic movement enhancer protein and a putative vector transmission factor was not detected in N. benthamiana after several passages even though systemic infection was observed, raising fundamental questions about the role of this segment in the systemic spread in several hosts.
- MeSH
- genom virový * genetika MeSH
- Hemiptera virologie MeSH
- jedlá semena virologie MeSH
- nemoci rostlin virologie MeSH
- rostlinné viry * genetika MeSH
- viry mozaiky * genetika MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Norsko MeSH
- Švédsko MeSH
The Campylobacter jejuni-host interaction may be affected by the host's gut microbiota through competitive exclusion, metabolites, or modification of the immune response. To understand this interaction, C. jejuni colonization and local immune responses were compared in chickens with different gut microbiota compositions. Birds were treated with an antibiotic cocktail (AT) (experiments 1 and 2) or raised under germfree (GF) conditions (experiment 3). At 18 days posthatch (dph), they were orally inoculated either with 104 CFU of C. jejuni or with diluent. Cecal as well as systemic C. jejuni colonization, T- and B-cell numbers in the gut, and gut-associated tissue were compared between the different groups. Significantly higher numbers of CFU of C. jejuni were detected in the cecal contents of AT and GF birds, with higher colonization rates in spleen, liver, and ileum, than in birds with a conventional gut microbiota (P < 0.05). Significant upregulation of T and B lymphocyte numbers was detected in cecum, cecal tonsils, and bursa of Fabricius of AT or GF birds after C. jejuni inoculation compared to the respective controls (P < 0.05). This difference was less clear in birds with a conventional gut microbiota. Histopathological gut lesions were observed only in C. jejuni-inoculated AT and GF birds but not in microbiota-colonized C. jejuni-inoculated hatchmates. These results demonstrate that the gut microbiota may contribute to the control of C. jejuni colonization and prevent lesion development. Further studies are needed to identify key players of the gut microbiota and the mechanisms behind their protective role.
- MeSH
- antibakteriální látky farmakologie MeSH
- B-lymfocyty imunologie mikrobiologie MeSH
- bursa Fabricii účinky léků imunologie mikrobiologie MeSH
- Campylobacter jejuni účinky léků imunologie patogenita MeSH
- cékum účinky léků imunologie mikrobiologie MeSH
- gnotobiologické modely imunologie MeSH
- ileum účinky léků imunologie mikrobiologie MeSH
- interakce hostitele a patogenu imunologie MeSH
- játra účinky léků imunologie mikrobiologie MeSH
- kampylobakterové infekce imunologie mikrobiologie veterinární MeSH
- kur domácí MeSH
- mikrobiální interakce imunologie MeSH
- nemoci drůbeže imunologie mikrobiologie MeSH
- počet mikrobiálních kolonií MeSH
- slezina účinky léků imunologie mikrobiologie MeSH
- střevní mikroflóra imunologie MeSH
- T-lymfocyty imunologie mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH