scholarly journals Structural features of non-cellular tissues of the human body during ochronosis

2020 ◽  
Vol 27 (4) ◽  
pp. 46-52
Author(s):  
Svetlana N. Shatokhina ◽  
Vadim V. Zar ◽  
Mikhail V. Zar ◽  
Vladimir N. Shabalin

With the help of special methods of dehydration, the features of the structural organization of the solid phase of biological fluids of a patient with a rare genetic disease ochronosis were revealed. Three biological fluids were taken as material for the study: urine, blood serum, and synovial fluid. For the transfer of biological fluids into a solid phase, the methods of cuneiform and marginal dehydration (technology Litos-System) were used. The structure of the solid phase of biological fluids was studied using stereomicroscopy in white and polarized light, as well as in a dark field. It was found that the structures of the solid phase of biological fluids reflect the main clinical signs of ochronosis, and also contains information about concomitant pathological processes. Specific structures of the solid phase of patients with ochronosis can be used as diagnostic markers of this disease.

Author(s):  
U. Aebi ◽  
P. Rew ◽  
T.-T. Sun

Various types of intermediate-sized (10-nm) filaments have been found and described in many different cell types during the past few years. Despite the differences in the chemical composition among the different types of filaments, they all yield common structural features: they are usually up to several microns long and have a diameter of 7 to 10 nm; there is evidence that they are made of several 2 to 3.5 nm wide protofilaments which are helically wound around each other; the secondary structure of the polypeptides constituting the filaments is rich in ∞-helix. However a detailed description of their structural organization is lacking to date.


Author(s):  
С.Н. Шатохина ◽  
Н.А. Кузнецова ◽  
В.Н. Шабалин

Цель проведённого исследования состояла в оценке эффективности визуального анализа твёрдофазных структур спинномозговой жидкости для диагностики ранних форм нейросифилиса. Методы. Использован метод краевой дегидратации биологических жидкостей, входящий в состав авторской диагностической технологии «Литос-система». Диагностика раннего асимптомного нейросифилиса заключается в выявлении деструктивных образований в форме овалов в морфологической картине твёрдой фазы спинномозговой жидкости. Результаты. Проведён сравнительный анализ результатов исследования спинномозговой жидкости у 19 больных с подтверждённым диагнозом «ранний асимптомный нейросифилис», полученных традиционными лабораторными методами и методом краевой дегидратации. Выявлено, что локализация овалов внутри сферолитов указывает на длительность заболевания нейросифилисом менее трёх лет, а вне сферолитов - от трех до пяти лет. Заключение. Метод краевой дегидратации позволяет диагностировать ранний асимптомный нейросифилис по наличию деструктивных образований в форме овалов в морфологической картине твёрдой фазы спинномозговой жидкости. The aim of this study was to evaluate effectiveness of visual analysis of solid-phase structures in cerebrospinal fluid to diagnose early forms of neurosyphilis. Methods. We used a method of marginal dehydration of biological fluids as a part of the author’s diagnostic technology, Litos-System. Early asymptomatic neurosyphilis is diagnosed based on detection of destructive, oval-shaped formations in the morphological picture of cerebrospinal fluid solid phase. Results. Data from analyses of cerebrospinal fluid performed with traditional laboratory methods and the method of marginal dehydration were compared for 19 patients with documented diagnosis of early asymptomatic neurosyphilis. A localization of ovals within spherulites indicated a less than a three-year duration of neurosyphilis while a localization outside spherulites indicated a duration of three to five years. Conclusion. The method of marginal dehydration allows detecting early asymptomatic neurosyphilis based on the presence of destructive, oval-shaped formations in the morphological picture of cerebrospinal fluid solid phase.


1991 ◽  
Vol 56 (2) ◽  
pp. 491-498 ◽  
Author(s):  
Bernard Lammek ◽  
Izabela Derdowska ◽  
Tomasz M. Wierzba ◽  
Witold Juzwa

In an attempt to determine some of the structural features in position 1 that account for V1 antagonism, four new analogues of arginine-vasopressin were synthesized and the effect of the modifications on the vasoconstrictor activity was checked using isolated mesenteric arterial vessels of rats. The protected precursors required for these analogues were synthesized by a solid phase method of peptide synthesis. One of the reported analogues, namely [1-(4-mercapto-4-tetrahydrothiopyraneacetic acid)., 2-O-methyltyrosine, 8-arginine]vasopressin appears to be a potent competitive antagonist of the vasoconstrictor effect by AVP.


Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2194
Author(s):  
Kamil Łuczykowski ◽  
Natalia Warmuzińska ◽  
Sylwia Operacz ◽  
Iga Stryjak ◽  
Joanna Bogusiewicz ◽  
...  

Bladder cancer (BC) is a common malignancy of the urinary system and a leading cause of death worldwide. In this work, untargeted metabolomic profiling of biological fluids is presented as a non-invasive tool for bladder cancer biomarker discovery as a first step towards developing superior methods for detection, treatment, and prevention well as to further our current understanding of this disease. In this study, urine samples from 24 healthy volunteers and 24 BC patients were subjected to metabolomic profiling using high throughput solid-phase microextraction (SPME) in thin-film format and reversed-phase high-performance liquid chromatography coupled with a Q Exactive Focus Orbitrap mass spectrometer. The chemometric analysis enabled the selection of metabolites contributing to the observed separation of BC patients from the control group. Relevant differences were demonstrated for phenylalanine metabolism compounds, i.e., benzoic acid, hippuric acid, and 4-hydroxycinnamic acid. Furthermore, compounds involved in the metabolism of histidine, beta-alanine, and glycerophospholipids were also identified. Thin-film SPME can be efficiently used as an alternative approach to other traditional urine sample preparation methods, demonstrating the SPME technique as a simple and efficient tool for urinary metabolomics research. Moreover, this study’s results may support a better understanding of bladder cancer development and progression mechanisms.


Molecules ◽  
2021 ◽  
Vol 26 (1) ◽  
pp. 197
Author(s):  
Iván Ramos-Tomillero ◽  
Marisa K. Sánchez ◽  
Hortensia Rodríguez ◽  
Fernando Albericio

Using the classical Ugi four-component reaction to fuse an amine, ketone, carboxylic acid, and isocyanide, here we prepared a short library of N-alkylated α,α-dialkylglycine derivatives. Due to the polyfunctionality of the dipeptidic scaffold, this highly steric hindered system shows an interesting acidolytic cleavage of the C-terminal amide. In this regard, we studied the structure-acid lability relationship of the C-terminal amide bond (cyclohexylamide) of N-alkylated α,α-dialkylglycine amides 1a–n in acidic media and, afterward, it was established that the most important structural features related to its cleavage. Then, it was demonstrated that electron-donating effects in the aromatic amines, flexible acyl chains (Gly) at the N-terminal and the introduction of cyclic compounds into dipeptide scaffolds, increased the rate of acidolysis. All these effects are related to the ease with which the oxazolonium ion intermediate forms and they promote the proximity of the central carbonyl group to the C-terminal amide, resulting in C-terminal amide cleavage. Consequently, these findings could be applied for the design of new protecting groups, handles for solid-phase synthesis, and linkers for conjugation, due to its easily modulable and the fact that it allows to fine tune its acid-lability.


2017 ◽  
Vol 91 (21) ◽  
Author(s):  
Allison Kraus ◽  
Gregory J. Raymond ◽  
Brent Race ◽  
Katrina J. Campbell ◽  
Andrew G. Hughson ◽  
...  

ABSTRACT Accumulation of fibrillar protein aggregates is a hallmark of many diseases. While numerous proteins form fibrils by prion-like seeded polymerization in vitro, only some are transmissible and pathogenic in vivo. To probe the structural features that confer transmissibility to prion protein (PrP) fibrils, we have analyzed synthetic PrP amyloids with or without the human prion disease-associated P102L mutation. The formation of infectious prions from PrP molecules in vitro has required cofactors and/or unphysiological denaturing conditions. Here, we demonstrate that, under physiologically compatible conditions without cofactors, the P102L mutation in recombinant hamster PrP promoted prion formation when seeded by minute amounts of scrapie prions in vitro. Surprisingly, combination of the P102L mutation with charge-neutralizing substitutions of four nearby lysines promoted spontaneous prion formation. When inoculated into hamsters, both of these types of synthetic prions initiated substantial accumulation of prion seeding activity and protease-resistant PrP without transmissible spongiform encephalopathy (TSE) clinical signs or notable glial activation. Our evidence suggests that PrP's centrally located proline and lysine residues act as conformational switches in the in vitro formation of transmissible PrP amyloids. IMPORTANCE Many diseases involve the damaging accumulation of specific misfolded proteins in thread-like aggregates. These threads (fibrils) are capable of growing on the ends by seeding the refolding and incorporation of the normal form of the given protein. In many cases such aggregates can be infectious and propagate like prions when transmitted from one individual host to another. Some transmitted aggregates can cause fatal disease, as with human iatrogenic prion diseases, while other aggregates appear to be relatively innocuous. The factors that distinguish infectious and pathogenic protein aggregates from more innocuous ones are poorly understood. Here we have compared the combined effects of prion seeding and mutations of prion protein (PrP) on the structure and transmission properties of synthetic PrP aggregates. Our results highlight the influence of specific sequence features in the normally unstructured region of PrP that influence the infectious and neuropathogenic properties of PrP-derived aggregates.


The solid phase of the compound 2'-methoxy-2 : 4 : 4 : 7 : 4'- pentamethylflavan differs in many respects from normally crystalline materials, yet is not amorphous. It tends to form spherical masses which exhibit no regular crystal boundaries, even when seen under the microscope. The solid melts over a range of up to 3° C and the actual temperatures at which melting begins and ends vary according to the thermal treatment previously received by the specimen. The temperature at which the melt starts to solidify on cooling is always several degrees below the melting range; this is not due to normal supercooling. Solidification from the melt presents several other interesting features, including some rhythmic effects. Variations in the external conditions during solidification can give rise to three superficially different forms of the solid phase. The solid-liquid and liquid-solid transitions have been followed by measurements of density, rigidity and dielectric constant, all of which give further indications of the diffuse nature of the melting process and the existence of hysteresis between melting and solidifica­tion. These effects recall the behaviour of some crystalline high polymers and examination of solid methoxypentamethylflavan by polarized light, X-rays and electron microscopy has revealed further analogies with such materials. It is tentatively concluded that the solid is composed of submicroscopic crystalline regions which are organized into larger spherulitic aggregates, but no definite explanations of the failure of the compound to form macroscopic crystals or of the similarities between it and polymers seem possible at present.


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