[Study of mutual synchronization of self-oscillations of cellular density in skin lesions caused by psoriasis based on paracrine regulation of epidermal proliferation with participation of T-lymphocytes].

This paper represents the results of research of mutual synchronization of self-oscillations of epidermal cellular density in skin lesions caused by psoriasis under strong limited noise conditions by the method of computing experiment. As an initial model the system of three ordinary nonlinear differential equations, presumably describing principles of paracrine regulation of epidermal proliferation with participation of populations functionally activated by CD4+/CD8+ T-lymphocytes is used. The results of research have shown, that if epidermal proliferation is considered as an attribute determining pathomorphologic features of dermatoses, synchronization can appear to be responsible for development of linear, annular, arcuate, geographical, and also the limited and common forms of disease. It is shown, that strong noise is capable of providing different duration for clinical manifestation of ensembles of synchronously connected lesions of psoriatic skin within several days, as to phase slip - it is up to several tens of days, and distinction of physical parameters - it is from several hours up to about several days.

[A mathematical model of paracrine regulation of the proliferative activity of epidermis with the participation of T-lymphocytes].

A mathematical model of paracrine regulation of the proliferative activity of epidermis in the foci of skin lesions in psoriatic patients is presented. The model simulates the participation of skin-infiltrating activated T-lymphocytes as cellular regulators of apoptosis of proliferating keratinocytes. It allows one to describe all basic phases of the development of the focus of psoriatic lesion: the beginning of formation, a long stable or periodic manifestation, and the resolution of lesion and its involution to clinically uninvolved and normal skin. The model shows also the possibility of a spasmodic (triggering) transition of a pathological focus of lesion from the condition of remission to a new exacerbation and vice versa, which is a characteristic feature of the disease.

[Numerical modeling of mutual synchronization of self-oscillations of the epidermal proliferative activity in lesions of psoriatic skin].

The results of numerical modeling of mutual synchronization of self-oscillations of epidermal hyperproliferation in foci of lesions in psoriasis are presented. It is shown that this phenomenon enables one to explain some facts of development of the disease such as: (1) figured arrangement of pathological elements; (2) unexpected exacerbation of the process a short time after the treatment; (3) persistence of lesions in a limited region of the skin or, vice versa, their fast distribution throughout the surface of the body of a patient.

Synchronization of oscillations of proliferation of keratinocytes in psoriatic skin by external periodic force: a mathematical model.

A mathematical model of mitotic activity of epidermis in normal skin and skin afflicted with psoriasis is presented as a system of two autonomous nonlinear differential equations. Its qualitative analysis was carried out and numerical solutions were obtained at the parameter values corresponding to these states. It was shown that in the norm, a single stable equilibrium of a "focus" type exists in the system; whereas in psoriasis, owing to an increase in the growing fraction, hyperproliferation, and enhanced migration of interacting keratinocytes, a stable limit cycle arises from the state of unstable focus. In this paper we also report on the results of computer modeling of synchronization of self-excited oscillations of keratinocyte population density in psoriatic lesions by an external periodic force. This synchronization is viewed as a possible mechanism of the clinically observed dependence of psoriasis course on some natural factors of cyclic nature.

[The scaling method of spatial distribution of keratinocytes in the basal layer of epidermis in norm and during the development of psoriatic lesion]. / Skeilingovaia model' prostranstvennogo raspredeleniia keratinotsitov basal'nogo sloia épidermisa v norme i pri razvitii psoriaticheskogo ochaga porazheniia.

On the basis of the modern conceptions postulating that the growing layer of normal epidermis contains two populations of keratinocytes differing greatly in the rate of mitotic division (stem and transient cells), a hypothesis was proposed that explains the reason for the establishment of the portion of the proliferating fraction close to 60%. A relationship between this value and the distribution of keratinocytes of the basal layer in space was demonstrated, and formulae for its calculation were derived. Possible pathways of the transition from the normal spatial configuration to the distribution typical for the focal lesion in psoriasis were analyzed when all stem cells begin to divide vigorously, and the size of the population of transient cells is 100%.

[Mathematical model of proliferative activity in epidermis of the normal skin and of the skin afflicted by psoriasis]. / Matematicheskaia model' proliferativnoi aktivnosti épidermisa v normal'noi i psoriaticheski izmenennoi kozhe.

A mathematical model of the mitotic activity of epidermis in norm and psoriasis is presented, which consists of a system of two autonomous nonlinear differential equations. A qualitative analysis of the model was done, and numerical solutions at the parameter values corresponding to these state were obtained. It was shown that, in norm, the system can exist only in one stationary equilibrium state of the "focus" type, and in psoriasis, due to an increase in the growing fraction, hyperproliferation, and enhanced migration of keratinocytes, a stable limiting cycle arises from the state of an unstable focus. The existence of two stable states (focus and the limiting cycle) is regulated by a parameter that describes the inhibition of division of maturing cells of suprabasal epidermal layers by the intrinsic tissue-specific transmitters of mitosis of G1-keilon type. The model is consistent with experimental data on the kinetics of cell proliferation in the epidermis in norm and psoriasis and the clinical course of the disease.

In vivo optical coherence tomography imaging of human skin: norm and pathology.

BACKGROUND/AIMS: Since the majority of skin diseases are known to be accompanied by structural alterations, research efforts are focused on the development of various novel diagnostic techniques capable of providing in vivo information on the skin structure. An essential parameter here is spatial resolution. In this paper we demonstrate the capabilities of optical coherence tomography (OCT) in detecting in vivo specific features of thin and thick skin. A particular focus is made on the identification of OCT patterns typical of certain pathological processes in skin, by performing parallel histological and tomographical studies. METHODS: To obtain images of the skin, we used a compact fiber OCT system developed at the Institute of Applied Physics of the Russian Academy of Sciences. A low coherence source (superluminescent diode) operated at a wavelength of 1280 nm; the output power was 0.5-2 mW. This power is low enough to conform to the ANSI safety standards for light exposure. The in-depth resolution limited by the spectral bandwidth (40-50 nm) of the probing light was approximately 20 &mgr;m. The lateral resolution determined by the probe light focusing ranged from 15 to 30 &mgr;m. In this series of experiments the maximum depth of imaging did not extend beyond 1.5 mm. Obtaining images of skin regions 2-6 mm long took 2-4 s. OCT capabilities for imaging normal skin of different localization and some skin diseases were studied in 12 healthy volunteers and 24 patients. RESULTS: OCT imaging of the skin can detect in vivo such general pathological reactions of the human body as active inflammation and necrosis. OCT is useful for in vivo diagnosis of some specific processes in the skin, including hyperkeratosis, parakeratosis and formation of intradermal cavities. OCT imaging is noninvasive and therefore allows frequent multifocal examination of skin without any adverse effects. OCT can perform monitoring of disease progress and recovery in the course of therapy. Morphometric studies, measurements of the depth and extension of skin pathology within the human body can be easily performed by OCT. CONCLUSIONS: OCT allows imaging of subsurface soft tissues with the spatial resolution of 15-20 &mgr;m, a resolution one order of magnitude higher than that provided by other clinically available noninvasive diagnostic techniques. An imaging depth of up to 1.5-2 mm, given by current OCT technology, is sufficient to examine the skin. Real time OCT imaging can provide information not only on the structure, but also on some specific features in the functional state, of tissues. OCT imaging is a noninvasive technique, i.e., OCT does not cause trauma and has no side effects since it utilizes radiation in the near infrared wavelength range at a power as low as 1 mW.