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MOLECULAR AND CELLULAR MECHANISMS OF INFLAMMATORY REACTION
FERENCIK, M.
Inflammation is a complex stereotypical reaction of the body expressing the response to damage of its cells and/or vascularized tissues. It is the body's reaction to invasion by an infectious agent, antigen chalenge or even just physical, chemical, or traumatic damage. The development of inflammatory reactions is controlled by a number of cellular and molecular components. Leukocytes (namely neutrophils and macrophages) belong to the key inflammatory cells. Their accumulation in inflamed tissue results from adhesive interactions between leukocytes and endothelial cells within the microcirculation. The nature and magnitude of the adhesive interactions that take place within postcapillary venules are determined by a variety of factors, of which the contribution of different adhesion molecules (selectins, integrins, members of immunoglobulin superfamily) to leukocyte rolling, adherence, and emigration in venules is discussed. The main purpose of inflammation seems to be to bring fluids, proteins and cells from the blood into the damaged tissues for the elimination of injuring agent and triggering the healing and repairing processes. This is under the control of inflammation mediators which include vasoactive substances, proinflammatory and antiinflammatory cytokines, chemokines, acute phase reactants, bioactive lipids (prostanoids, platelet activating factor - PAF) and products of the plasma enzyme systems (complement, the coagulation clothing, kinin and fibrinolytic pathways) which are shortly reviewed. Several neuroendocrine hormones, neuropeptides, neurotransmitters and mainly glucocorticoids also play an important role of endogenous regulators of any inflammatory process. (Tab. 4, Fig. 1, Ref. 52.)
Key words: inflammation; neutrophils; leukocyte adhesion; selectins; integrins; proinflammatory and anti-inflammatory cytokines; chemokines; acute phase proteins; glucocorticoids.
Bratisl Lek Listy 1995; 96: 509-519
VASKULITIDY ANCA - IMUNOLOGICKE A KLINICKE ASPEKTY
SCHULZ, J.I.
The author reviews the opinions on vasculitis pathogenesis which is based on the direct noxa impact, active immunity process against the specific components of the vascular tissue and/or passive impact of the inflammatory process upon vessels. The detection is especially based on two most important ANCA tests, i.e. indirect immunofluorescence and ELISA. The author includes also the sensitivity and specificity of these examinations and their predictive value in progressive glomerulonephritis, Wegener's granulomatosis and other diseases. (Tab. 1, Ref. 20.)
Key words: vasculitis; ANCA; inflammation; predictive value.
Bratisl Lek Listy 1995; 96: 520-522
ADHESIVE MOLECULES AND CYTOKINES IN VASCULITIS
FUCIKOVA, T., TESAR, V., MASEK, J., BARTUNKOVA, J., RYCHLIK, I.
Renal vasculitis syndromes include particular characteristic changes in concentrations of some cytokines in plasma or urine. Preliminary results suggest that the systemic lupus erhythematodes with affliction of the kidneys is specifically concomitted by the increase in IL-8, both in plasma and urine. ANCA-positive renal vasculitis syndromes appear to coincide with a typical increase in the synthesis of interleukin-6 in the kidneys. We suggest that the monitoring of individual cytokine levels in plasma and urine will enable to study in greater detail the immunopathogenesis of renal vasculitis syndromes and the extent of local production of cytokines which may cause further progression of renal lesions. (Fig. 4, Tab. 1, Ref. 10.)
Key words: adhesive molecules; cytokines; vasculitis; ANCA.
Bratisl Lek Listy 1995; 96:523-527
DIAGNOSTIC AND PATHOGENETIC ROLE OF ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODIES IN VASCULITIS
BARTUNKOVA, J., TESAR, V., FUCIKOVA, T., JANATKOVA, I., ZABKA, J., KRYSTUFKOVA, O., RYCHLIK, I.
Objectives: The study represents a complex report on diagnostic
and pathogenic significance of antineutrophil cytoplasmic autoantibodies
(ANCA). Our report is founded on the results of our clinical and
experimental studies.
Methods: ANCA was examined by indirect immunofluorescence,
or ELISA-anti MPO. The data for evaluation of diagnostic ANCA
associations were gained by means of questionnaires. The experimental
part involved examination of the impact of sera containing ANCA
and monoclonal antibodies (MoAb) against proteinase 3 and control
MoaB specific for neutrophils.
Results: Within the course of 1 year we have examined 1010
samples, ANCA was found in 65 patients: 26 cases of systemic vasculitis,
12 cases of other autoimmune diseases, 9 cases of isolated glomerulonephritis,
7 cases of inflammatory intestinal diseases, 6 cases of ophtalmic
inflammatory diseases, and 6 cases of other diseases. Vasculitis
of small vessels found in our group of patients are concomitted
by ANCA positivity in 90 % (Wegener's granulomatosis 15/16, Churg-Strauss's
syndrome 3/5, MPA 9/9), vasculitis of medium vessels 12 % (classical
polyarteritis nodosa 1/2, Kawasaki disease 0/2, Henoch-Schonlein's
purpura 0/4, Takayasu's arteritis 1/4). The ANCA-containing sera
inhibit the candidacidal activity by 65 % in average. The inhibitory
impact is yielded by anti-proteinase MoAb, in contrast to the
control MoAb.
Conclusion: c-ANCA in high concentration is specific for
active form of Wegener's granulomatosis, other types of ANCA in
low titres are not of diagnostic value for vasculitis. ANCA is
concomitted especially by small vessels vasculitis. The proved
inhibition of microbicidal PMN activity by ANCA can participate
in some clinical signs of immunodef ficiencies in vasculitis.
(Tab. 5, Ref. 18.)
Key words: antineutrophil cytoplasmic autoantibodies; ANCA; diagnostic and pathogenetic significance.
Bratisl Lek Listy 1995; 96: 528-533
CLASSIFICATION AND PATHOGENESIS OF VASCULITIDES
LUKAC, J., ROVENSKY, J.
Vasculitis is a heterogeneous group of diseases which is characteristic
by inflammatory cellular infiltration of the vascular wall often
being concommited by fibrinoid necrosis. The pre-condition for
stating the diagnosis is the primary localization of inflammation
in the vascular wall. Affliction of vessels can be focal or segmental.
Focal vasculitis afflicts merely a part of the vessel's wall perimeter,
and aneurysms may develop. Segmental vasculitis refers to a lesion
of the entire perimeter of the vascular wall which often leads
to stenosis or occlusion of the vessel. Non-specific histologic
findings of perivascular infiltrates cannot be considered as evidence
of vasculitis. The authors present the classification of vasculitis,
its development and relation to etiopathogenesis of the disease,
including histopathology and clinical symptoms. (Fig. 1, Tab.
9, Ref.43.)
Key words: vasculitis classification; vasculitis pathogenesis; vasculitis.
Bratisl Lek Listy 1995; 96: 534-543
CORONARY VASCULITIS
STVRTINOVA, V.
It is generally accepted that myocardial ischemia, and its extreme
consequence, acute myocardial infarction, can result from transient
or permanent disproportion between myocardial oxygen demand and
coronary artery blood supply. Insufficient coronary artery blood
supply may have many reasons.
The aim of the study is to point to the clinical features of the
coronary vasculitides as well as to the diagnostic and therapeutic
possibilities. Coronary artery involvement in infectious angiitis,
in Takayasu's arteritis, in granulomatous giant cell arteritis,
in thromboangiitis obliterans, in polyarteritis nodosa, in Wegener's
granulomatosis and in Churg-Strauss syndrome is discussed.
The diagnosis of coronary vasculitis must be supposed in every
patient with primary or secondary vasculitis in whom chest pain
or cardiac failure appear. In young patients with clinical, electrocardiographic
or laboratory signs of coronary artery disease, especially in
absence of risk factors for atherosclerosis, the diagnosis of
coronary vasculitis must be considered in differential diagnosis.
(Fig. 4, Tab. 1, Ref. 32.)
Key words : coronary arteries; inflammation; vasculitis.
Bratisl Lek Listy 1995; 96: 544-551
THE ROLE OF ANGIOGRAPHY IN THE VASCULITIS DIAGNOSIS
LESNY, P.
A review of angiographic findings in vasculitides classified according to Lie is introduced. Angiography is an important investigation in angiitis that affects large, medium and visualisible small vessels. Its importance resides in 1. diagnosis, 2. selection of addequate therapeutic intervention. This work includes the description of angiographic findings in Takayasu's arteritis and Buerger's disease. (Fig. 4, Ref. 26.)
Key words: angiography; vasculitides; Takayasu's arteritis; thromboangiitis obliterans.
Bratisl Lek Listy 1995; 96: 552-557
DERMAL SYMPTOMS IN VASCULITIS
POCK, L., STORK, J., BECVAR, R.
Vasculitis has a very variable dermal manifestation. It includes purpura, pustules, bullae, ulcers, nodosits, pomphi etc. Dermal manifestation can represent the initial signs in systemic vasculitis and therefore its early clinical and histopathologic evaluation represents a presupposition for the determination of the subsequent examination route. The study gives information on general morphogenesis, principles of the correctly performed probatory excision, and clinical and histopathologic patterns of individual vasculitis types. (Tab. 2, Ref. 8.)
Key words: dermal vasculitis; probatory excision; histopathology; clinical manifestation; diagnosis; therapy.
Bratisl Lek Listy 1995; 96: 558-560
GENERAL THERAPEUTIC APPROACHES IN SYSTEMIC VASCULITIS
ROVENSKY, J., LUKAC, J., KOPECKY, S., MALIS, F., BOSMANSKY, K.
The paper presents general therapeutic principles applied in systemic vasculitis. Several factors may help to contain the clinical activity, such as the location and extent of the inflammatory process affecting the vascular system, the ultimate narrowing of the vascular lumen with subsequent ischemia of the affected tissue and organ. Treatment of vasculitis involves besides glucocorticoids not only cytotoxic drugs (cyclophosphamide, chlorambucil, methotrexate), and immunomodulatory therapeutic agents with immunosupressive action (cyclosporin A) but also other immunomodulatory drugs, as e.g. dialyzed homogenat of leukocytes (DHL), pentoxyphylline, hydrolytic enzymes, and monoclonal antibodies. The authors emphasize the importance of a complex approach in the management of systemic vasculitis. (Tab. 1, Ref. 36.)
Key words: systemic vasculitis; immunosupressive, immunomodulatory therapeutic agents; complex therapy.
Bratisl Lek Listy 1995; 96: 561-565
SYSTEMIC ENZYME THERAPY IN ANGIOLOGY
NOUZA, K.
The treatment of autoimmune and immune complex diseases of the
vascular bed consists - similarly as of immunopathologic processes
of other systems - in the use of risky immunosuppressive agents
and antiinflammatory as well as symptomatic therapy. In the article
the author informs about the possibility to use in these indications
(and in addition also in other angiologic diseases) the systemic
enzyme therapy, residing in the oral application of high-dosed
combinations of several animal and plant proteolytic enzymes.
About four tens years of positive medical empirical experience
have been supported by a concentrated sophisticated research and
approximately 150 clinical studies according to GCP. These revealed
in most autoimmune and immune complex diseases a surprisingly
high effectiveness and complete harmlessness of the enzyme therapy.
After the short introduction mentioning the important indications
for enzyme therapy in the field of clinical immunology, the major
attention is paid to the results of enzymotherapy in angiology.
Strong evidence indicates that enzymotherapy ameliorates the disturbed
composition and properties of blood and vessel walls, acts preventively
as well as therapeutically in thromboses, thromboflebitides and
consequences of venous insufficiency; it seems be prospective
in afflictions of arterial bed, including vasculitides and glomerulonephritides,
also.
The key feature of enzymotherapy is the immunomodulatory activity.
There exists a strong evidence for the favourable modulation of
pathogenic autoantibodies, inhibition of the neogenesis of immune
complexes and cleavage of their deposits, normalization of the
T cell system, network of cytokines, adhesion molecules and inflammatory
cascades. Besides the direct peptidolytic and proteolytic effects
of hydrolases, the indirect effects realized in the course of
interaction between the resorbed enzymes and their natural "partners"
- antiproteases (mainly alfa-2-macroglobulin) - have become a
topic of intensive research.
The author feels, that systemic enzyme therapy should become a
regular component of the treatment of immunopathologic processes
in general and of angiologic diseases specially. (Ref. 42.)
Key words: diseases of the vascular bed; systemic enzyme therapy.
Bratisl Lek Listy 1995; 96: 566-569
THE SURGICAL ASPECT IN BUERGER'S DISEASE
TRESKA, V., CECHURA, M.
Background: The Buerger's disease (BD) is known for more
than 100 years. It inflicts especially young men, smokers, at
the age of about 40 and manifests itself by ischemia in the periphery
of limbs which cannot be explained by precedent injury, embolism,
diabetes or hyperlipemia. The disease inflicts the medium or small
peripheral arteries of extremities. The occurrence of BD is most
frequent in the Mediterranean and East-Asian countries. The therapy
is so far symptomatic and is unsuccessful in cases when the patient
is reluctant to cease smoking.
Aim: The study is aimed at ascertainment of the results
of surgical therapy in 14 patients with BD hospitalized in the
Surgical Clinic FN in Plzen during the period from 1986 to 1995.
Methods: The average age of patients was 39.6±1.2
y. The ratio males/females was 13:1. All patients were smokers.
4 patients had a trophic defect in the periphery of the upper
and 11 of the lower limbs. 9 (64.3 %) patients displayed the Raynod's
phenomenon and seven (50 %) had thrombophlebitis. All patients
were treated conservatively (vasodilators, anticoagulants, antiaggregants,
corticoids, prostacyclins, nifedipine). Sympatectomy (lumbal,
upper thorax) was performed in 10 (71.4 %), and profundoplasty
in 2 patients (14.3 %).
Results: Conservative therapy, sympatectomy and revascularization
methods failed to have a long-term effect. Repeated hospitalization
of the patients was necessary, namely 7 times in average, and
limbs were amputated in high percentage of patients (50 %). However
in cases when patients ceased smoking, the disease withdrawed
or became stabilized.
Conclusion: Despite the fact that BD has become less frequent
in our population, it still disables young groups of patients.
The therapy is so far symptomatic and the successfulness of therapy
strongly depends on the patient's willingness to cooperate (cessation
of smoking) and as such it is often unsuccessful. The surgical
therapy, so far, fails to have a long-term effect and high percentage
of limb amputation is necessary. (Ref. 11.)
Key words: Buerger's disease; diagnosis; therapy.
Bratisl Lek Listy 1995; 96: 570-572