The challenges of the modern society and the growing demand of high-technology sectors of industrial production bring about a new phase in the development of organic synthesis. A cutting edge of ...modern synthetic methods is introduction of functional groups and more complex structural units into organic molecules with unprecedented control over the course of chemical transformation. Analysis of the state-of-the-art achievements in selective organic synthesis indicates the appearance of a new trend - the synthesis of organic molecules, biologically active compounds, pharmaceutical substances and smart materials with absolute selectivity. Most advanced approaches to organic synthesis anticipated in the near future can be defined as 'atomic precision' in chemical reactions. The present review considers selective methods of organic synthesis suitable for transformation of complex functionalized molecules under mild conditions. Selected key trends in the modern organic synthesis are considered including the preparation of organofluorine compounds, catalytic cross-coupling and oxidative cross-coupling reactions, atom-economic addition reactions, methathesis processes, oxidation and reduction reactions, synthesis of heterocyclic compounds, design of new homogeneous and heterogeneous catalytic systems, application of photocatalysis, scaling up synthetic procedures to industrial level and development of new approaches to investigation of mechanisms of catalytic reactions. The bibliography includes 840 references.
The study focuses on the effects of azithromycin on severity of ischemia/reperfusion myocardial injury during simulated systemic inflammatory response syndrome (SIRS) in primary visceral obesity ...(PVO). Total ischemia/reperfusion was modeled by Langendorff perfusion of isolated heart with following estimation of the size of myocardial infarction. SIRS was accompanied by an increase in blood levels of proinflammatory cytokines and LPS. Combination of PVO and SIRS produced no significant changes in the infarct size compared to the control. Administration of azithromycin to rats with PVO and SIRS resulted in pronounced alterations of biochemical and immunological parameters, although it did not affect the infarct size. In contrast, the use of tetracycline increased the size of myocardial infarction. This phenomenon should be taken into consideration in antimicrobial therapy.
Numerous experimental and clinical studies have shown the effectiveness of various probiotic strains in metabolic disorders, gastrointestinal and liver diseases, immune system pathology. The effects ...of probiotics on cardiovascular dysfunction are less well known. The development and validation of a new experimental model in rats, including obesity, acute colon inflammation and antibiotic-induced dysbiosis, with common characteristics of systemic inflammatory response syndrome (SIRS), became the basis for investigating the effects of probiotic drugs on myocardial resistance to ischemic-reperfusion injury (IRI) using an in vivo model of infarction after coronary occlusion. A 24% increase in myocardial infarction compared to intact animals (
p
< 0.05) and significant changes in leukogram, biochemical and immunological parameters were found in Wistar rats with SIRS modelling. Introduction of a mixture of strains of
Lactobacillus acidophilus
(LA-5) and
Bifidobacterium animalis
subsp.
lactis
(BB-12) to animals with SIRS reduced infarct size to a value close to the control. Rats treated with LA-5 and BB-12 also showed normalization of the leukocyte count, bile acids, transforming growth factor-β, interleukins: IL-1α, IL-2, IL-6, IL-8, tumor necrosis factor-α, lipopolysaccharide and monocyte chemoattractant protein-1 in blood in comparison with the SIRS group and with the groups treated with other probiotic strains. The obtained data convincingly show the prospects for further study of the cardiotropic potential of probiotic microorganisms in translational studies.
We studied the influence of recombinant IL-2 and brain-derived neurotrophic factor (BDNF) on the size of the myocardial necrosis zone of rats with systemic inflammatory response syndrome (SIRS). A ...significant increase in the necrosis zone and the levels of proinflammatory cytokines was revealed in animals with SIRS in comparison with the control. The administration of IL-2 to animals with SIRS significantly reduced the size of the necrosis zone, which was paralleled by a pronounced increase in IL-2 and BDNF in comparison with the corresponding parameters in rats with SIRS that did not receive IL-2. Administration of BDNF to animals with SIRS was followed by normalization of TNFα and IL-1α levels, but did not lead to a decrease in the size of the necrosis zone.
We studied the effect of combined antimicrobial therapy with amoxicillin, metronidazole, and clarithromycin on the severity of ischemia/reperfusion myocardial injury in Wistar rats with alimentary ...obesity and acute inflammation of the large intestine. General ischemia/reperfusion was reproduced on Langendorff-perfused isolated hearts and infarct size was estimated. Acute inflammation of the large intestine was accompanied by an increase in the blood levels of proinflammatory cytokines. The presence of obesity and acute inflammation of the large intestine did not significantly affect the infarct size in comparison with the control. Administration of antimicrobial drugs to animals with obesity and acute inflammation of the large intestine led to a significant increase in the infarct size, which should be considered when prescribing antimicrobial therapy to patients with comorbidity.
Aim:
to study myocardial resistance to ischemia-reperfusion and behavioural responses taking into account sex differences in rats in an experimental model of obesity and systemic inflammatory ...response syndrome (SIRS).
Materials and methods
: experiments were performed on male and female Sprague–Dawley (SD) rats at the age of three months with primary visceral obesity (PVO). SIRS was modelled by a single rectal injection of acetic acid, followed by intragastrical administration of the antimicrobial drugs mixture (AMP) for 3 days. The other group of rats was treated orally with a mixture of probiotic strains
Lactobacillus acidophilus
(LA-5) and
Bifidobacterium animalis subsp. lactis
(BB-12), at a CFU concentration of 10
8
per animal for 8 days after the simulation of SIRS. Behavioural tests “open field” (OFT), “elevated plus maze” (EPM), “light–dark box” (LDB) were performed alternately before the end of the experiment. At the end of the experiment, the levels of tumor necrosis factor-α, interleukin-2, leptin, lipopolysaccharide, transforming growth factor-β and brain neurotrophic factor in the blood were assessed, hemodynamic parameters and myocardial resistance to ischemia-reperfusion were studied on an isolated heart model.
Results:
a higher food intake per 1 g of body mass and more pronounced thrombocytosis and granulocytosis were observed in the group of female rats, as compared to males after the SIRS modelling. Female rats had higher serum levels of tumor necrosis factor-α, leptin, interleukin-2, and lipopolysaccharide than males, as well as lower levels of transforming growth factor-β. In male rats, probiotic modulation of orientation and exploratory behaviour and anxiety was observed whereas in female rats the rate of conditioned reflexes formation was corrected by probiotics. There were no significant differences in hemodynamic parameters, as well as in the size of the infarction between the studied groups.
Conclusion:
the data obtained indicate a significant role of sex hormones in the pathogenesis of SIRS, as well as a different response of females and males to probiotic therapy. The results generally show a higher intensity of compensatory-adaptive reactions and a greater efficiency of probiotic correction of SIRS in female rats compared to males. At the same time, the size of the infarction did not differ between females and males.
For the first time, the synthesis of organosilicon derivatives of dialkyl1benzothieno3,2-b1-benzothiophene (BTBT) capable of forming a semiconducting monolayer at the water-air interface is reported. ...Self-assembled monolayer organic field-effect transistors prepared from these materials using the Langmuir-Blodgett technique showed high hole mobilities and excellent air stability.
Within the concept of a gut–heart microbiome axis, new works are emerging to support the efficacy of probiotic strains to increase myocardial resistance to ischemia–reperfusion injury (IRI) in ...polymorbidity. The question remains open whether the presence of live probiotic bacteria is a prerequisite for the implementation of their cardioprotective effect. This work was aimed to determine the manifestation of the cardioprotective effect of live and pasteurized
Lactobacillus acidophilus
(LA-5) and
Bifidobacterium animalis subsp. lactis
(BB-12) probiotic strains in rats with systemic inflammatory response syndrome (SIRS). Myocardial resistance to IRI was assessed using an in vivo model of left coronary artery (LCA) occlusion–reperfusion. Experiments were performed on male Wistar rats with an improved conventional status with visceral obesity, chemically induced colitis, and antibiotic-induced gut dysbiosis, which co-provided SIRS formation against the background of oral administration of live or inactivated probiotic bacteria. Infarct size in the group with a SIRS model (SIRS group) was significantly larger than in the control group 43% (39; 44) vs. 31% (28; 35) (
p
< 0.05). In the SIRS group administered with inactivated probiotic bacteria, infarct size did not differ from that in the SIRS group and was significantly higher than in the control 45% (37; 48) (
p
< 0.05). At the same time, infarct size in the group administered with live probiotics did not differ from that in the control group 32% (28; 37). Conclusions: (1) live and inactivated probiotic strains of
Lactobacillus acidophilus
and
Bifidobacterium animalis subsp. lactis
exert different effects on rats with SIRS, (2) cardioprotective effect is only provided by live lacto- and bifidobacteria in animals with SIRS.
Experimental medicine provides the scientific community with a plethora of information on therapeutic efficacy of probiotic strains. However, from the point of view of evidence-based medicine, the ...list of disorders controlled by probiotics is limited to antibiotic-associated diarrhea in adults and children,
Clostridium
difficile
-associated diarrhea, acute infectious diarrhea in children and adults, eradication therapy, ulcerative colitis and irritable bowel syndrome. Recently, these indications are also amended by well-validated clinical guidelines for the usage of probiotic preparations, in order to modulate immunity. Given the permeability of gastrointestinal and immune system barriers for pathogenic and opportunistic microbiota, it seems logical to assume the effectiveness of probiotics as potential symbiotic regulators of nervous and cardiovascular systems. It should also be taken into account that metabolic disorders, e.g., obesity, with a low-intensity inflammatory response and characteristic cytokine pattern, are acquired as a gain of human civilization. In this regard, we propose a scientific hypothesis about the effectiveness of probiotic microbial strains in increasing myocardial resistance to ischemic-reperfusion injury, due to their ability to block individual links of the cytokine cascade during the development of inflammatory response, for its subsequent translation into clinical practice.
The development and validation of a new experimental model of systemic inflammatory response syndrome (SIRS) in male Wistar rats, including obesity, acute inflammatory process of the colon, and antibiotic-induced dysbiosis, became basic to the study of efficacy of probiotic drugs in terms of myocardial resistance to ischemicreperfusion injury (IRI). Rats with SIRS showed a significantly increased size of the infarction area (+28%) upon experiments with isolated perfused heart under global ischemia-reperfusion conditions. Significant changes in the leukocyte formula and immunological parameters associated with SIRS were corrected by introduction of a mixture of probiotic strains
L. acidophilus
(LA-5) and
B. animalis subsp. lactis
(BB-12), and the isolated strain
L. delbrueckii
TS1-06. In both groups with probiotic correction, there was a decrease in the infarction area compared to the SIRS group. General and specific changes in IL-2, transforming growth factor-b (TGF-b) and tumor necrosis factor-a (TNFa) were noted. The reduction of myocardial infarction by probiotics may be related to the blocking of first-order cytokines, which leads to a «break» of proinflammatory cascade. A need for in-depth study of cardioprotective mechanisms mediated by probiotics was confirmed due to their potential usage as a symbiotic alternative to biological drugs which block the main pro-inflammatory cytokines.
Friedel-Crafts acylation of tetrathienoacene (TTA) followed by a reduction reaction resulting in various octyl-substituted TTA derivatives is described for the first time. Varying conditions of the ...acylation reaction allowed control over the formation of mono- or diketones, which were further reduced to mono- or dialkyls. It was shown that an alkyl group can be introduced either in α, β, or both positions of TTA in a controllable way. Optical, thermal, electrochemical and semiconducting properties of the mono and dioctyl substituted derivatives of TTA are presented. Small and wide-angle diffraction investigations made it possible to attribute the
P
2 monoclinic crystal structure for
C8-TTA-C8
and mesophase existence for
C8-TTA
at room temperature. Top-contact bottom gate OFETs with a
C8-TTA-C8
active layer fabricated by vacuum deposition or solution processing showed similar characteristics pointing out its good processability.
Friedel-Crafts acylation of tetrathienoacene (TTA) followed by a reduction reaction led to promising organic semiconductor
C8-TTA-C8
, which was preliminarily tested as an active layer in OFETs.
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