Laser-irradiating infrared attenuated total reflection spectroscopy of articular cartilage: Potential and challenges for diagnosing osteoarthritis.

Objective: A prototype infrared attenuated total reflection (IR-ATR) laser spectroscopic system designed for in vivo classification of human cartilage tissue according to its histological health status during arthroscopic surgery is presented. Prior to real-world in vivo applications, this so-called osteoarthritis (OA) scanner has been tested at in vitro conditions revealing the challenges associated with complex sample matrices and the accordingly obtained sparse spectral datasets. Methods: In vitro studies on human knee cartilage samples at different contact pressures (i.e., 0.2-0.5 â€‹MPa) allowed recording cartilage degeneration characteristic IR signatures comparable to in vivo conditions with high temporal resolution. Afterwards, the cartilage samples were assessed based on the clinically acknowledged osteoarthritis cartilage histopathology assessment (OARSI) system and correlated with the obtained sparse IR data. Results: Amide and carbohydrate signal behavior was observed to be almost identical between the obtained sparse IR data and previously measured FTIR data used for sparse partial least squares discriminant analysis (SPLSDA) to identify the spectral regions relevant to cartilage condition. Contact pressures between 0.3 and 0.4 â€‹MPa seem to provide the best sparse IR spectra for cylindrical (d â€‹= â€‹3 â€‹mm) probe tips. Conclusion: Laser-irradiating IR-ATR spectroscopy is a promising analytical technique for future arthroscopic applications to differentiate healthy and osteoarthritic cartilage tissue. However, this study also revealed that the flexible connection between the laser-based analyzer and the arthroscopic ATR-probe via IR-transparent fiberoptic cables may affect the robustness of the obtained IR data and requires further improvements.

[GENETIC ASPECTS OF RESISTANCE TO MALARIA (REVIEW)].

Malaria is one of the most important and common infectious diseases in the world. The world health organization estimates 225 million malaria cases worldwide. Malaria is one of the strongest selective factors affecting the human genotype. The greatest pressure of malaria pathogens had on the inhabitants of the tropical belt, in which invasion was the main factor of genetic selection. As a result, there were genetic diseases such as sickle cell anemia, thalassemia, glucose-6-phosphate dehydrogenase deficiency and others. An important role in the pathogenesis of malaria is the stage of penetration of the parasite of malarial Plasmodium into the erythrocyte. Changes in the structure of surface antigens of red blood cells may contribute to or reduce the effectiveness of invasion. Genetic polymorphism associated with the pathogenesis and characteristics of the malaria clinic is also important in the development of malaria resistance. Understanding the genetic changes associated with red blood cell disorders and pathogenesis can provide insights into the development of new strategies for malaria treatment and prevention.

[STRUCTURAL, MOLECULAR AND FUNCTIONAL FEATURES OF NEMATODE SURFACES AND THE POSSIBILITY OF ANTHELMINTIC DRUGS DEVELOPMENT (REVIEW)].

Helminthiases caused by parasitic nematodes are widespread in different regions of the world. The main adaptation for overcoming adverse conditions is a barrier properties of the cuticle surface structure, which differs from the membrane teguments of trematodes and cestodes. Different types of nematodes have specific structural and biochemical adaptations at different stages of their life cycle. While creating specific areas of habitat and nutrition, some types of parasites change the morphology and functioning of the host tissues. Ascaris suum and Caenorabditis elegans were widely used as model organisms in the study of genetics, biochemistry of nematodes. Studying of biochemistry and molecular biology of structural components of nematode surfaces is important for development of effective and safe anthelmintic drugs. The differences in the structure and functioning of transport enzymes of parasites and humans will help to create effective specific inhibitors and anthelmintic remedies. An important point of application of anthelmintic drugs can serve as inorganic ions transport proteins in the membranes of the surfaces. Glycolipids of cuticle contribute to the evasion from the host immune system, protecting the surface proteins from degradation by proteases. Study of helminth surfaces makes an important contribution to the development of anthelmintic drugs and vaccines, for helminthiasis treat.

[CHARACTERISTICS OF PARASITIC PROTOZOA METABOLISM AND POSSIBILITIES OF ANTIPROTOZOA DRUG DEVELOPMENT (REVIEW)].

One of the most poorly studied areas of protozoology is metabolic processes of parasitic protozoa. Study of the biochemistry of parasites required for the development of effective chemotherapy of protozoal diseases. Some amitochondrial parasites of humans, such as Giardia intestinalis, Entamoeba histolytica, Trichomonas sp., living in an environment with low oxygen content, have specialized cellular organelles-hydrogenosomes (like mitochondria provide cells with simple energy). The study of the functioning of these organelles allows us to consider them as targets for the development of аntiprotozoal drugs. The target for chemotherapy in the treatment of trypanosomiasis can be processes related to the characteristics of the glycolytic pathway or a decrease in the level of energy substrate, such as glucose. This leads to a rapid decrease in ATP levels in the cell of the parasite, an overall loss of mobility and disappearance of trypanosomes from the bloodstream of the infected host. Also, glucose transporters located in the membrane of the parasite can be targets for drugs.

[(IMPACT OF LUNGWORM INFESTATION ON THE BIOCHEMICAL PARAMETERS OF ANIMALS DURING COMBINATION TREATMENT WITH ALBENDAZOLE AND T- AND B-ACTIVIN)].

Lungworm infection is caused by a Dictyocaulus filaria nematode parasitizing the bronchi and bronchioles of sheep and goats. Various anthelmintics, including albendazole, levamisole, fenbendazole, ivermectins, and others, are used to treat the animals. The aim of this investigation was to study the impact of lungworm infestation on the biochemical parameters of animals during combination treatment with albendazole and T- and B-activin. Experiments were carried out in 20 uninfected mongrel lambs aged 4-5 months. Infectious D.filaria larvae were given with water to 15 lambs once orally at a dose of 1000 larvae per head. 5 uninfected lambs served as a control group. The time course of changes in serum bio- chemical parameters was studied in animals. Treatment with Albena in combination with T- and B-activin in lambs ex- perimentally infested with lungworm was found to restore their biochemical reactivity. After sheep treatment with Albena alone, biochemical parameters were noted to tend to normalize, but their normal full recovery did not take place.

[Nonantibiotic properties of macrolides and their role in modulation of the inflammatory reaction].

Macrolides is one of the most interesting and promising classes of antibiotics, which occupy one of the first places in the world in the frequency of clinical use. In recent years, new facts have reported about specific features of the mechanism of action and pharmacodynamics of macrolides, in particular, with respect to their anti-inflammatory effect. Unfortunately, many therapists and pharmacists are not familiar with recent advanced in the clinical and pharmacological evidence concerning extra-antibiotic properties characteristic of some macrolides. Macrolides increase defensive mechanisms of the body against infection at the first stage of their action and suppress inflammation at the next stages, which leads to faster resolution of a disease. The immunomodulating properties of macrolides are also discussed and require further investigation. Good prospects are related with combined therapy, in which antibiotics are used jointly with drugs potentiating their extra-antibiotic effect and overwhelming negative effects on the body. This approach will significantly improve the efficiency of therapy, reduce the risk of side effects, and reduce the cost of treatment.

[Genetic resistance to malaria].

Genetic resistance to malaria is associated with various genetic factors, including erythrocytic variability and variability of the genes involved into the pathogenetic process. Some genetic anomalies resulted from selective malaria pressure, which brought into existence different forms of hemoglobinopathies, glucose-6-phosphate dehydrogenase deficiency, and no Duffy antigens, and ovalocytosis, etc., which ensured varying malaria resistance. Cell adhesion is a major factor in the pathogenesis of malaria. Adhesion molecules express on the cellular membranes of the endothelium, platelets, macrophages, red blood cells and serve as binding receptors for membrane proteins PFRMP-1 of P. falciparum. Polymorphism of the CD36, ICAM-1, and PECAM1 genes can lower binding to blood vessel endothelial cells, which reduces the number of clinical forms of malaria. The high serum TNF-alpha level that is caused by mutation in the promoter of the TNF-alpha gene is associated with cerebral malaria. TNF-alpha enhances the endothelial expression of adhesion molecules, by increasing the adhesion of infected erythrocytes, including that in cerebral capillaries, by inducing in patients local thrombosis and inflammation with release of the cytokines--TNF-alpha. The products of inflammatory infiltrates attack the endothelium, by leading to the imbibition of plasma and erythrocytes in brain tissue and causing a cerebral form of malaria.

[Molecular receptors of taste agents].

All representatives of higher eukaryotes can probably differentially perceive nutrients and poisonous substances. Molecular mechanisms of transduction of taste information have been best studied for mammals and for the fruit fly Drosophila. Here, we consider receptor mechanisms and conjugated primary signal processes of stimulation of taste receptor cells by stimuli of various taste modalities.

[Identification of cytochromes P450 in the human liver microsomes by mass spectrometry].

Proteomic approaches have been used for detection and identification of cytochromes P450 from highly-purified membrane preparations of human liver. These included the protein separation by 2D- and/or 1D-electrophoresis and molecular scanning of a SDS-PAGE gel fragment in the range of 45-66 kD (this area corresponds molecular weights of cytochromes P450). The analysis of protein content was statistically evaluated by means of original 1D-ZOOMER software package which allowed to carry out processing of mass spectra mixture instead of individual mass spectra used by standard techniques. In the range of 45-66 kDa we identified 13 microsomal membrane proteins including 11 cytochromes P450, namely CYPs 1A2, 1B1, 2A6, 2E1, 2C8, 2C9, 2C10, 2D6, 3A4, 4A11, 4F2. The microsomal samples were characterized by the enzymatic assays using the marker substrates for CYP1A, 2B, 3A4, 2C and 2E1. The 7-methoxy- and 7-ethoxyresorufin-O-dealkylase activities (i.e. the marker activities for cytochromes P450 1A1/1A2, respectively) and the erythromycin-N-demethylase activity (i.e. the marker activity for cytochrome P450 3A4) are lowered in pathology compared to these activities in norm. At the same time the benzyloxyresorufin-O-debenzylase activity (which characterizes the total activity of CYP2B and CYP2C), the activities of CYP2E1 (methanol), 7-pentoxyresorufin-O-dealkylation (CYP2B), 7-ethoxy- and 7-methoxycoumarin-O-dealkylases (CYP2B1) did not change. On the basis of the results obtained efficiency of a combination proteomic and biochemical analyses for inventory cytochromes P450 and revealing of their level expression is shown, and opportunities of mass spectrometry for a quantitative estimation of proteins are discussed.

[Antioxidant properties of novel preparations--bioflavonoid derivatives and tannins]. / Sopostavlenie antioksidantnykh svoistv novykh preparatov, proizvodnykh bioflavonoidov i dubil'nykh veshchestv.

New medicinal plant preparations of polyphenol nature, representing the derivatives of bioflavonoids (piflamin) and ellagotannins (altan and ellagic acid) were experimentally studied. The drugs exhibited antioxidant properties, which were manifested by inhibition of a pathological lipid peroxidation, restoration of the functional activity of the antioxidant system components, and stabilization of the hepatocyte membranes.

[A morphological study of blastocysts in lower monkeys using light microscopy]. / Izuchenie morfologii blastotsist nizshikh obez'ian s pomoshch'iu svetovoi mikroskopii.

The paper shows a high infection of some species of nonhuman primates with blastocysts. Lower rates of infection with this pathogen were observed in younger animals. The blastocysts isolated from Macaca mulatta were microscopically analyzed. The findings indicate a great morphological similarity between the blastocysts of primates and those of man (Blastocystis hominis).

[The antimutagenic action of a preparation of a species-nonspecific interferon]. / Antimutagennoe deistvie preparata vidonespetsifichnogo interferona.

The human gene-engineering gamma-interferon agent gammaferon (GF) is demonstrated to lower the level of chromosomal aberrations and release of cyclophosphamide-induced micronuclei in murine bone marrow cells. A model is suggested for regulating the ratio of single to multiple chromosomal aberrations induced by cyclophosphamide by altering the antioxidative status of the body. With this model, it was shown that the antimutagenic effects of GF were caused by two factors: the antioxidative effect of the corresponding placebo and the unknown (but none antioxidative) effect of gamma-interferon itself. Erythrocytic resistance to in vitro oxidative disturbance in the Fe2+/system was used as an integral measure of the body's antioxidative status.

[A visceral form of Rendu-Osler-Weber syndrome]. / Vistseral'naia forma bolezni Randiu-Oslera-Vebera.

A case of a visceral pattern (with primary liver injury) of the Rendu-Osler-Weber disease is described with emphasis on the diagnostic difficulties due to the absence of external symptoms of disease and hemorrhage. Stress is laid on the importance of making liver biopsy in the diagnosis of this pattern of teleangioectatic disease. It is assumed that microcirculatory disorders in the liver provoked by the development of teleangioectasia are essential factors in the formation of liver cirrhosis in visceral pattern of the Rendu-Osler-Weber disease.

[Functional role of the processes of an identified edible snail neuron]. / Funktsional'naia rol' otrostkov identifitsirovannogo neirona vinogradnoi ulitki.

Electrophysiological and morphological studies of an identified giant neurone of the snail Helix pomatia showed that the neurone PPa4 possesses a large receptive field and axones entering peripheric nerves. It is suggested that this neurone is an output integrative link of the mollusc's CNS. Through various types of spike activity PPa4 may exert a tonic or a phasic effect on neurones of the peripheric nervous system or a direct influence on effector organs of the mantle and pneumostome.