Endovascular Recanalization and Carotid Stenting: The New Approach to Restore Cerebral Perfusion during Aortic Dissection.

A type A aortic dissection (TAAD) is a dangerous condition requiring emergency surgery. Due to the similarity of the symptoms of cerebral malperfusion in TAAD and the signs of ischemic stroke, a differential diagnosis of these diseases is not always available. Patients with TAAD after cerebral malperfusion can have a neurological deficit. Thrombolysis is performed in this case. It can worsen the patient's condition and increase the risk of mortality and disability. The aim of the study is to evaluate the new approach to restoring cerebral perfusion during aortic dissection. This approach includes endovascular recanalization and carotid stenting. METHODS: Two clinical cases of TAAD complicated by cerebral malperfusion are described. The first patient is 73 years old and was admitted as planned to perform transcatheter aortic valve implantation (TAVI) for grade III aortic stenosis. The patient underwent transcatheter aortic valve implantation (TAVI) on the second day after admission. The second patient is 60 years old and was hospitalized by an ambulance with strong hypertension and ischemia. The surgical correction of aortic dissection was postponed until the neurological status assessment in both patients. RESULTS: The surgery to correct the aorta dissection was deemed inappropriate. The carotid arteries have been reanalyzed, and cerebral perfusion has been restored in a short time in both patients. CONCLUSION: Acute bilateral internal carotid occlusion is a potentially fatal TAAD outcome. Emergency endovascular recanalization and carotid stenting may be considered one of the few ways to restore cerebral perfusion.

The First Reciprocal Activities of Chiral Peptide Pharmaceuticals: Thymogen and Thymodepressin, as Examples.

Peptides show high promise in the targeting and intracellular delivery of next-generation biotherapeutics. The main limitation is peptides' susceptibility to proteolysis in biological systems. Numerous strategies have been developed to overcome this challenge by chemically enhancing the resistance to proteolysis. In nature, amino acids, except glycine, are found in L- and D-enantiomers. The change from one form to the other will change the primary structure of polypeptides and proteins and may affect their function and biological activity. Given the inherent chiral nature of biological systems and their high enantiomeric selectivity, there is rising interest in manipulating the chirality of polypeptides to enhance their biomolecular interactions. In this review, we discuss the first examples of up-and-down homeostasis regulation by two enantiomeric drugs: immunostimulant Thymogen (L-Glu-L-Trp) and immunosuppressor Thymodepressin (D-Glu(D-Trp)). This study shows the perspective of exploring chirality to remove the chiral wall between L- and D-biomolecules. The selected clinical result will be discussed.

Spectrum of Surgical Site Infection Pathogens in Chronic Infectious Spondylitis Requiring Revision Surgery: A 5-Year Cohort Study.

Background: Spectrum monitoring of the pathogen in spondylitis patients plays a key role in preventing infectious complications of spinal reconstructions in chronic spondylitis (CS) and in the treatment of surgical site infection (SSI). The aim of this study is to characterize the spectrum of SSI pathogens in CS requiring revision surgery. Methods: The primary cohort encompassed 569 surgical patients with infectious CS. In 99 patients (61 men and 38 women) requiring revision surgical interventions due to SSI, continuous microbiological monitoring of the pathogens was conducted. The average age of the patients was 63 ± 14 years. The vast majority of the patients underwent surgery on a set of multilevel (two or more spinal-motor segments) lesions. Lesions of the lumbar spine were more often noted, and lesions of the thoracic, thoracolumbar, and cervical spine sections were less often noted. This study included all patients operated on within the scope of revision spinal reconstructions in connection with the development of infection of the surgical area over the period from January 2018 to December 2022. Inclusion criteria were etiologically verified spondylitis, age of 18 years or older, and follow-up of 6 months or more. Results: The average rate of revision surgery due to SSI was 17.4%. Germ detection from the material of vertebral localization was noted in 48.3% and pathogen strains were isolated in urine in 60.8%, in decubital ulcers in 23.9%, and in hemoculture in 15.2% of all study patients. Aseptic, deep SSI was detected in 10.1%. Gram-positive, multidrug-resistant, and Gram-negative bacteria with extreme resistance prevailed in the microbiological landscape of late SSI, early, and delayed Gram-positive strains without drug resistance. Conclusions: Infectious etiology of spondylitis is associated with a significantly higher frequency of SSI. In the absence of a positive result from bacteriological examination of the vertebral localization material, it is advisable to conduct blood, decubital ulcer discharge, and urine sampling.

Molecular Markers of Early Immune Response in Tuberculosis: Prospects of Application in Predictive Medicine.

Tuberculosis (TB) remains an important public health problem and one of the leading causes of death. Individuals with latent tuberculosis infection (LTBI) have an increased risk of developing active TB. The problem of the diagnosis of the various stages of TB and the identification of infected patients in the early stages has not yet been solved. The existing tests (the tuberculin skin test and the interferon-gamma release assay) are useful to distinguish between active and latent infections. But these tests cannot be used to predict the development of active TB in individuals with LTBI. The purpose of this review was to analyze the extant data of the interaction of M. tuberculosis with immune cells and identify molecular predictive markers and markers of the early stages of TB. An analysis of more than 90 sources from the literature allowed us to determine various subpopulations of immune cells involved in the pathogenesis of TB, namely, macrophages, dendritic cells, B lymphocytes, T helper cells, cytotoxic T lymphocytes, and NK cells. The key molecular markers of the immune response to M. tuberculosis are cytokines (IL-1ß, IL-6, IL-8, IL-10, IL-12, IL-17, IL-22b, IFNÉ£, TNFa, and TGFß), matrix metalloproteinases (MMP-1, MMP-3, and MMP-9), and their inhibitors (TIMP-1, TIMP-2, TIMP-3, and TIMP-4). It is supposed that these molecules could be used as biomarkers to characterize different stages of TB infection, to evaluate the effectiveness of its treatment, and as targets of pharmacotherapy.

Pulmonary Sarcoidosis: Experimental Models and Perspectives of Molecular Diagnostics Using Quantum Dots.

Sarcoidosis is a complex inflammatory multisystem disease of unknown etiology that is characterised by epithelioid cell granulomatous lesions affecting various organs, mainly the lungs. In general, sarcoidosis is asymptomatic, but some cases result in severe complications and organ failure. So far, no accurate and validated modelling for clinical and pathohistological manifestations of sarcoidosis is suggested. Moreover, knowledge about disease-specific diagnostic markers for sarcoidosis is scarce. For instance, pulmonary granulomatosis is associated with the upregulated production of proinflammatory molecules: TNF-α, IL-6, CXCL1, CCL2, CCL18, CD163, serum angiotensin-converting enzyme (sACE), lysozyme, neopterin, and serum amyloid A (SAA). Quantum dots (QDs) are widely applied for molecular diagnostics of various diseases. QDs are semiconductor nanoparticles of a few nanometres in size, made from ZnS, CdS, ZnSe, etc., with unique physical and chemical properties that are useful for the labelling and detection in biological experiments. QDs can conjugate with various antibodies or oligonucleotides, allowing for high-sensitivity detection of various targets in organs and cells. Our review describes existing experimental models for sarcoidosis (in vitro, in vivo, and in silico), their advantages and restrictions, as well as the physical properties of quantum dots and their potential applications in the molecular diagnostics of sarcoidosis. The most promising experimental models include mice with TSC2 deletion and an in silico multiscale computational model of sarcoidosis (SarcoidSim), developed using transcriptomics and flow cytometry of human sarcoid biopsies. Both models are most efficient to test different candidate drugs for sarcoidosis.

Characterization of electron donor sites on Al2O3 surface.

Formation of radical anions after adsorption of 1,3,5-trinitrobenzene (TNB) on electron donor sites of fully oxidized Al(2)O(3) samples with different phase compositions is studied by EPR. It is shown that the maximum concentration of the radical anions does not substantially depend on the choice of solvent and reaction temperature, and can be used to measure the total concentration of the donor sites. The donor sites are observed in almost the same concentration about 5 × 10(16) m(-2) on all alumina polymorphs except for α-Al(2)O(3). The formation rate of the TNB radical anions and the activation energy of this process are found to depend on the donor properties of the solvent. The EPR in situ experiments showed that a substantial amount of the adsorbate forming a liquid phase is required for generation of the radical anions. These results prove that the sites measured by the formation of the TNB radical anions are not genuine electron donor sites capable of direct electron transfer to the adsorbed TNB molecules. A model of the observed paramagnetic species based on the obtained experimental data and the results of quantum chemical simulations is suggested. According to this model, a TNB radical anion substitutes a hydroxyl group forming a neutral ion pair with a surface aluminum cation. The suggested mechanism for the formation of such ion pairs involves the migration of simple radicals and does not require long-distance charge separation. It is supposed that the donor site where the process is initiated includes a negatively charged surface hydroxyl group.