Role of reactive oxygen species (ROS) in patients with erythema migrans, an early manifestation of Lyme borreliosis.

BACKGROUND: Lyme borreliosis is a tick-transmitted, chronic, zoogenous disease caused by Borrelia burgdorferi spirochete. The clinical picture of Lyme disease is characterized by the variety of tissue and organ involvement and differing severity of symptoms. One of the pathogenic symptoms of early Lyme disease is a skin lesion called erythema migrans. MATERIAL AND METHODS: The purpose of our research was to estimate the parameters of the antioxidant system and the concentration of lipid peroxidation products in the plasma of patients with erythema migrans (EM). The parameters measured included the activity levels of superoxide dismutase (SOD) according to Sykes, gluthatione reductase (GSSG-R) according to Mize and Langdon, glutathione peroxidase (GSH-Px) according to Paglia and Valentine; the concentrations of malondialdehyde (MDA) were examined by means of a Bioxytech LPO-586 kit. The total sulphydryl groups (-SH) according to Ellman and reduced glutathione (GSH) were measured using a Bioxytech GSH-400 test in plasma samples collected from 20 patients with EM aged from 19 to 50, taken before (examination 1) and after (examination 2) therapy with amoxycycline. The control group consisted of 8 healthy people. RESULTS: The results of our examinations prove that beta-lactamase antibiotic therapy brings non-enzymatic antioxidant parameters to control values, though the treatment causes no change in enzymatic antioxidant parameters, resulting in the further activation of free radicals. CONCLUSIONS: In patients with Erythema migrans, the decreased capability to reduce lipid superoxidants leads to maintaining a high concentration of membrane lipid peroxidation products.

[Estimation of platelet counts and their morphological parameters in patients infected by borrelia burgdorferi]. / Ocena liczby plytek i ich parametrów morfologicznych u chorych zakazonych Borrelia burgdorferi.

Platelet counts and their morphologic parameters in patients with Lyme borreliosis before and after antibiotic therapy (4 weeks of treatment) were estimated. 30 patients aged 17-60, x = 41 were evaluated: 7 with Erythema migrans, 3 patients with neuroborreliosis in the from Lymphocytic meningitis and 20 ones with Lyme arthritis. Control group consisted of 19 healthy persons aged 34-52, x = 43. Hematologic analyser Coulter MAXM was used for testing PLT, MPV, PCT and PDW. The results indicated that patients with Lyme boreliosis have decreasing platelet count with simultaneously increasing their volume in comparison with healthy control. It may result from the involement of platelets in defense mechanisms of infected host. The decrease of platelet count after the antibiotic treatment in comparison with the control group may be the reflection of influence of antibiotic treatment on thrombopoesis.

[Epidemiologic aspect of lyme borreliosis among the inhabitants of Podlasie Province]. / Wybrane aspekty epidemiologiczne boreliozy z Lyme wsród mieszkanców województwa podlaskiego.

UNLABELLED: The aim of this study was to evaluate Lyme borreliosis morbidity among the inhabitants of Podlasie Province in the years of 1996-2000. MATERIAL AND METHODS: The new cases of Lyme borreliosis reported in the years of 1996-2000 in Podlasie Province were analyzed. The analysis included the data from Mz-56 and Mz-57 forms and the information from epidemiologic investigations sent to Regional Sanitary and Epidemiologic Station in Bialystok. In 1996-2000, screening examinations were carried out in the same group of 358 forestry workers including 44 (12.29%) females and 314 (87.71%) males aged from 21 to 64 (x = 41.2) years. Immunoenzymatic test of ELISA Borrelia recombinant IgM and IgG by Biomedica firm (Austria) were used to detect B. burgdorferi antibodies. RESULTS: In 1996-2000, 4933 of borreliosis cases were registered in Poland including 1377 (27.91%) in Podlasie Province. The morbidity rate in Podlasie province ranged from 15.05% in 1996 year to 21.29% in 2000 year of the whole country morbidity. At the same time, the incidence rate in Podlasie Province ranged from 9.09 in 1996 to 32.2 in 2000 year and was 6.72-fold higher than the incidence rate in the whole country. In Eastern and Central region of the province, 80.54% of cases were registered whereas, 14.09% by the Lakeside of Augustów and Suwalki only 5.37% in the western region of the province. It was proved that the morbidity increased in proportion to the age of patients (41.39% of patients were at the age of 30-49) and it decreased only above the age of 60. Thus, Lyme borreliosis affects mainly people at working age. The increase in B. burgdorferi antibody detectability was noticed in the population of forestry workers; it was detected in 38.55% in 1995 and in 2000 in 43.56% of the examined. Interestingly, 81 people infected with B.b in 1995-2000 included 74 men and only 7 women, supporting the statement that B.b infection affects mainly working professionals and the risk increases with the practice. CONCLUSIONS: Our studies indicate that Lyme borreliosis is a serious health problem among the inhabitants of Podlasie Province which is an endemic area for Ixodes ricinus ticks infected with B. burgdorferi spirochete.

[Proinflammatory cytokines in humoral immune response]. / Cytokiny prozapalne w odpowiedzi humoralnej.

Proinflammatory cytokines secreted by cells involved in inflammatory process play a key role in the regulation of immune responses, both cellular and humoral immune response. Through their influence on T-helper lymphocytes and antigen presenting cells including lymphocytes B, they induce secretion of secondary cytokines and, in cooperation with them, promote activation and proliferation of lymphocytes B and production of variety of classes of immunoglobulins. Cytokines interact with their specific receptors which usually occur both in membrane bound and soluble form. The purpose of this article was to evaluate the relationships between primary cytokines such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) and other cytokines, lymphocytes T-helper and lymphocytes B in the light of current opinions regarding this matter.

[Selected aspects of immunopathogenesis in Lyme disease]. / Wybrane zagadnienia immunopatogenezy choroby z Lyme.

Abilities of B. burgdorferi to infect and induce illness is connected with immunopathogenic factors as: immunomodulatory elements of tick saliva abilities of B. burgdorferi to move in extracellular matrix, connecting and activation of proteolitic zymogen, inducing endothelium to production of adhesive molecules, chemokines and acute phase proteins. Important elements in pathogenesis and course of Lyme disease are organ tropism, producing by lymphocytes T proinflammatory cytokines (Th1 and Th2 profile), phagocytic abilities of infected organisms. In pathogenesis of chronic and recurrent cases difficult to treat is essential is survive of metabolic inactive bacteria, antigens B. burgdorferi as form "blebs", cystic L-form or insoluble complexes antigen-antibody or possibility of intracellular survive of B. burgdorferi. Tissue and organs damage is caused not only directly by B. burgdorferi antigens. Undoubtedly in the late stages there are immunologic disregulation and molecular mimicry. In some cases important are concommitant other infections. All this factors and results of therapy have influence on prognosis of Lyme disease. Knowledge of pathogenesis of Lyme disease has an important meaning in interpretation of laboratory tests and estimation of clinical signs and choosing of treatment.

[Neurologic syndromes in Lyme disease]. / Neurologiczne postacie choroby z Lyme.

Lyme borreliosis, multisystem disease, when involve neurologic system is named neuroborrelosis. Symptomatology of neuroborreliosis is rich and various. Difficulties in recognition are connected usually with long period from tick bite to late neurological signs. Any headache and psychiatric disorder in the course of Lyme disease could be an early manifestation of invasion of the CNS by the spirochaetes. Each part of neurologic system could be involved. The most common clinical picture of neuroborreliosis is meningitis with cranial or peripheral neuropathies connected with radiculalgia, less common are encephalitis and myelitis, neuropathies and polyneuropathies, encephalopathies. Encephalomyelitis is the most serious form of neuroborreliosis. From the pathophysiologic point of view all cranial and peripheral neuropathies are forms of mononeuritis multiplex. Vasculitis and autoimmunology processes are present. Encephalopathy is due to neuroimmunomodulators, like lymphokines and by toxico-metabolic effect could be connected with each form of systemic borreliosis. Spheroplast L-form of borrelia could be responsible for difficulties with their eradication. Diagnosis of neuroborreliosis is based on culturing of B. burgdorferi from CSF, detection of specific antispirochaetal antibodies produced in subarachnoid space, detection of activated lymphocytes, other antigens detection in CSF (also after dissociation of complexes) or borrelial DNA sequences.

[Actual diagnostic possibilities of Lyme borreliosis]. / Aktualne mozliwosci diagnostyki boreliozy z Lyme.

Recognising of Lyme disease is based on epidemiology investigation, clinical manifestation of disease and results of diagnostic laboratory tests. Direct methods as isolation and culturing of Borrelia burgdorferi are very difficult and expensive. Depends on clinical stage PCR could be very useful but not often used. The other methods are based on detection of specific antispirochaetal antibodies produced in compartments or detection of antigens B. burgdorferi.

Subpopulations of the peripheral lymphocytes in the early clinical forms of Lyme disease.

The evaluation of the changes of lymphocytes: T(CD3), B (CD19), subpopulations CD4, CD8, active lymphocytes CD3 + HLA-DR+, lymphocytes with the receptor for IL2(CD3 + CD25+), NK cells as well as the CD4/CD8 ratio in 30 patients with the early localized (group I n = 7) and early disseminated (group II n = 23) type of Lyme disease, before (examination 1) and after the antibiotic therapy (examination 2) was performed. Group III was composed of 90 healthy people. Measurements were carried out in an COULTER EPIC XL cytoflowmeter, using Becton Dickinson antibodies. Statistical analysis was performed using AnStat software. In the examined groups, a decrease of the subpopulations of CD4, CD8 lymphocytes in comparison with healthy subjects was revealed, as well as a decrease of the CD4/CD8 ratio after treatment. A considerably lower percentage value of active lymphocytes CD3 + HLA-DR+ in both groups and the reduction of the NK subpopulation before and after treatment of early disseminated Lyme disease in comparison with healthy people was observed. The higher percentage values of the lymphocytes with IL-2 receptor were not statistically significant. The indicated essential changes in the subpopulations of T lymphocytes, characterized by a decrease before the antibiotic therapy and by the tendency towards an increase after that therapy of the percentage of CD4, CD8, NK and CD3 + HLA-DR+ lymphocytes in peripheral blood, point out their role in the immunopathogenesis of the Lyme disease. The absence of the complete normalization of the examined parameters after the treatment, on the one hand, may provide evidence for some inertia of the elements of the immune system, on the other hand can also result from too short antibiotic therapy and maintenance of the antigenic stimulation.

Analysis of some peripheral blood lymphocyte subsets in relation to Borrelia burgdorferi antibodies in patients with Lyme disease.

The aim of our study was to evaluate the changes in T (CD3), B(CD19) lymphocytes, CD4 and CD8 subsets, activated CD3+ HLA-DR+ lymphocytes, lymphocytes with receptor for IL-2 (CD3+CD25), NK cells as well as the rate of CD4/CD8 in 30 patients with recognized Lyme disease, before and after antibiotic therapy. Patients were divided into the following groups: Group I n = 9--without detected specific antibodies against B. burgdorferi and with clinical recognition of EM(erythema migrans). Group II n = 10--with increased IgM production, with a clinical form of Lyme arthritis and neuroborreliosis. Group III n = 11--with increased IgG anti B. burgdorferi production, with clinical recognition of Lyme arthritis. The results were compared with the results obtained in the control group consisting of 90 healthy people. The measurements were performed in the flow cytometer COULTER EPI XL with Becton Dickinson antibodies. The antibodies against B. burgdorferi were detected by means of ELISA method using Dako, Biomedica and Biocom kits. The statistic analysis was performed with AnStat Program. The changes in lymphocyte subsets were characterised by the decrease in the percentage of CD4, CD8, NK and CD3+HLA-DR+ lymphocytes in peripheral blood before treatment with later tendency to increase. The results show that the lag phase of antibodies production coincides with high activity of lymphocytes (group I). The significant level of antibodies in IgM class induced by the collaboration of T and B cells was found in the group II. In the group III, in which antibodies in IgG class predominated, the changes in lymphocyte subsets were less intensive. The results of our investigations indicate that the immune response in Lyme disease develops mainly with the participation of both cellular and humoral response which is involved in both the defense against and the pathogenesis of the disease.

[Herpes simplex encephalitis]. / Opryszczkowe zapalenie mózgu.

Herpes simplex virus infection of the central nervous system is still a significant cause of morbidity and often mortality. Changes of central nervous system are results of primary infection or activation of latent HSV-1, HSV-2. Neurological deficits often follow encephalitis herpetica. The application of PCR is prompt and specific diagnosis of herpes simplex virus infections of the brain. Advances in treatment herpes simplex encephalitis with acyclovir have improved outcome.

[Selected lymphocyte subsets in Lime borreliosis: a preliminary study]. / Wybrane subpopulacje limfocytów w boreliozie z Lyme--doniesienie wstepne.

Observation of percentages changes of lymphocytes (CD19), T(CD3), subsets CD4, CD8, NK cells, activated lymphocytes with fenotype CD3+HLA-DR, CD4/CD8 rate in Lyme borreliosis was carried out before (I examination) and after antibioticotherapy (II examination). 30 patients in aged 17-60 (x = 41) with recognition of erythema migrans(EM), Lyme arthritis(LA) and neuroborreliosis(NB) were examined. Epidemiological, clinical diagnosis was confirm by the presence of antibodies in ELISA test. Lymphocytes and their subsets, NK cells were signed and measured by flow cytometric immunophenotyping in Coulter EPIX XL with Becton-Dickinson antibodies twice: before and after treatment. Ampicillin, ceftriaxon or cefotaxim was applied during 4 weeks. AnStat program was used in statistic analysis. Value CD3 (x = 72.54) in I test was higher than control (x = 69.3), but CD19 (x = 13.2) was lower than control (x = 12.9). In II examination we stated CD19 (x = 9.48) progressive significant decreased in comparison to I examination. Percentage CD4 in II examination (x = 42) was lower than control (x = 45.8). Subset of CD8 had lower value in I examination (x = 28.03), as in II (x = 30.72) in comparison with control (x = 34.2). We showed lower CD4/CD8 (x = 1.40) rate after treatment than control (x = 2.67). We showed lower percentage NK cells after treatment (x = 13.5) than control. We also found lower percentage activated subsets T cells with phenotype CD3+HLA-DR before (x = 4.78) and after treatment (x = 4.03) compared with control (x = 7.27). No statistical changes in subsets with receptor for IL-2 before and after treatment was shown. In the course of active infection B.burgdorferi essential changes in lymphocytes subsets are observed. Decreased percentages of CD4, CD8, NK and CD3+HLA-DR+ in whole blood indicate their important role in immunopathogenesis of Lyme borreliosis. Lack of normalization of investigated parameters after treatment can be caused by inertion of elements immunologic system, as well as too short antibioticotherapies.

[Mental disorders in the course of neuroborreliosis: own observation]. / Zaburzenia psychiczne w przebiegu neuroboreliozy--obserwacje wlasne.

Three cases of psychic disorders in the course of Lyme borreliosis were described. Two cases were connected with Lyme meningitis, one of them with chronic Lyme arthritis. These cases were described to discuss the possible occurrence of mental disturbances in the course of Lyme borreliosis, directly or indirectly connected with the central nervous system.

[Levels of proinflammatory cytokines: IL-1, IL-6, IL-8, TNF-alpha and receptor IL-6R in Lyme borreliosis]. / Stezenie cytokin prozapalnych: IL-1, IL-6, IL-8, TNF-alfa oraz receptora IL-6R w boreliozie z Lyme.

We estimated serum concentrations of cytokines IL-1, IL-6, IL-8, TNF-alfa and IL-6R of patients with diagnosed Lyme disease treated with beta-lactam antibiotics. Detection of proinflammatory cytokines was performed in ELISA tests. The examination was performed before and after treatment. Comparison with control group stated statistically significant higher concentration of IL-1 and IL-6 before and after treatment. There were no differences in concentration of TNF-alfa, IL-8 and IL-6R. Comparing concentrations of cytokines before and after treatment there was no differences either. Lack of changes in concentration of proinflammatory cytokines during beta-lactam therapy could be explained by too short period of therapy or immunologic background of inflammatory process in Lyme disease which was only initiated by spirochete Borrelia burgdorferi.

[The time of maintainance of positive serologic results among patients operated on echinococcal liver cysts]. / Czas utrzymywania sie dodatnich wyników badan serologicznych u osób operowanych z rozpoznaniem bablowicy watroby - obserwacje wlasne.

The purpose of this work was to analyse results of serologie examinations and complaints reported by patients who were operated on echinococcal liver cysts. The analysis was conducted on patients who were qualified to surgical removal of echionococcal liver cysts. Persons who were analysed answered the questionaires and 11 of them send sera for serologie examination. The questionaires consisted of questions about time since operation, complaints before and after operation abdomen pains, distensions, vomits, exanthema, weakness, headaches). Results showed that patient were from 1 to 6 years after operation. Among 11 who send sera 18% results were negative (2 and 6 years after operation) and 82% was positive. Analysis of 15 questionnaires showed that majority of patients still had the complaints that were present before operation.

[Neurologic borreliosis]. / Neuroborelioza.

Any headache in the course of Lyme disease could be an early manifestation of invasion of the CNS by spirochaetes. The most characteristic symptoms of early neuroborreliosis are meningitis with cranial or peripheral neuropathies connected with radiculopathies, less common are encephalitis and myelitis, neuropathies, polyneuropathies, encephalopathies. Encephalomyelitis is the most serious form of neuroborreliosis. From the pathophysiologic point of view all cranial and peripheral neuropathies are forms of mononeuritis multiplex. Encephalopathy is due to neuroimmunomodulators, like lymphokins and or by toxico-metabolic effect could be connected with each form of systemic borreliosis. Certain diagnosis of neuroborreliosis is based on culturing of B. burgdorferi from CSF, detection of specific antispirochaetal antibodies produced in the subarachnoid space, detection of activated lymphocytes B producing specific antibodies, detection in CSF of other antigens of B. burgdorferi or DNA sequences.

[Lasting hearing loss in the course of neuro-borreliosis]. / Trwale uszkodzenie sluchu w przebiegu neuroboreliozy.

Lyme borreliosis is spirochetal disease that frequently affects the nervous system months or years after infection giving rise to a varied clinical picture named neuro-borreliosis. We report a case of 47 year old female with progressing hearing loss, tinnitus, paraparesis and ataxia. The disease was beginning six month earlier by weakness of the lower limbs associated with hearing loss. The patient did not remember to be exposed to ticks and did not recall the presence of erythema migrans, arthritis or other systemic signs. CSF was with mononuclear pleocytosis and protein concentration over 600 mg%. Firstly patient was unsuccessfully treated like encephalomeningitis with tbc etiology. Next cerebrospinal fluid analysis showed presence of antibodies against Borrelia burgdorferi in IgG and IgM class. IgG antibodies in serum were founded. Audiometry electric responses from brain stem showed sensorineural hearing loss. Therapy with ceftriaxone was successful. Because negative tick bile history and many signs from different parts of CNS, relationship of this spirochetal infection and severe otolaryngological and neurological disease was firstly difficult to recognition.

[Otoneurologic state estimation 2 years after tick-borne encephalitis]. / Ocena stanu otoneurologicznego po 2 latach od przebycia kleszczowego zapalenia mózgu.

In this paper an attempt is described to estimate the incidence and frequency of neurologic and otologic symptoms among patients two years after TBE. We examined 43 persons of both sexes aged 17-58. The most frequent complaints were: headache--34.9%, equilibrium problems--37.2%, buzzing in the ears--27.9%, hearing problems--23.3%, memory problems--25.6%. Decrease of throat reflexes was stated in 3 (7%) and pseudobulbaris symptoms in 2 (4.6%), weakness of muscles in 4 (9.3%). In audiometric examination decrease of hearing was stated in 8 persons (18.5%). We registered nystagmus: spontaneous--4.6-7%, gaze--13.9-18.6%, positional-T, mainly Nylen I and III type-18.6-25.6%. Pathologic recording in the eye-tracking pattern test was shown in 7 (16.3%) persons. Asymmetry of optokinetic nystagmus was stated in 6 (13.9%) examined persons. Asymmetry in caloric test was proved in 25.5% of examined persons.

[Lymphocytic meningitis with the involvement of the skull in the course of spinal cord neoplasm simulating neuroborreliosis. Case report]. / Limfocytarne zapalenie opon mózgowo-rdzeniowych z zajeciem nn. czaszkowych w przebiegu procesu nowotworowego kanalu kregowego imitujace neuroborelioze. Opis przypadku.

UNLABELLED: We describe a case of 48 year old male patient treated in the Department of Parasitic Diseases and Neuroinfections AMB with suspected neuroborreliosis. CLINICAL SYMPTOMS: lymphocytic meningitis with cranial neuropathies n. VII palsy and radiculitis after numerous tick bites in endemic area--indicated neuroborreliosis. Because there was no effect of antibiotic therapy and lack antibodies against B-burgdorferi in serum and CSF we excluded neuroborreliosis. Developing neuropathies III-XII, increasing cytosis and protein concentration, radiculalgia and difficulties in walking, cachexia made us think of tbc etiology. Patient failed to improve after anti-tbc treatment. CT and MR showed presence of neoplasmatic masses in spinal canal. In cytologic examination "neoplasma malignum male differentiatum probabiliter metastaticum" was found. Primary focus of neoplasmatic process was not found.

[Albumin and immunoglobulin levels in cerebrospinal fluid and serum in tick borne meningoencephalitis]. / Stezenie albumin i immunoglobulin w plynie mózgowo-rdzeniowym i w surowicy w zapaleniach opon mózgowo-rdzeniowych o etiologii kleszczowej.

The levels of albumin and immunoglobulins G, A, M were determined by using nephelometry technique in the cerebrospinal fluid and serum in 14 adults with tick borne meningoencephalitis at the beginning and after four weeks of disease. Intra blood-brain synthesis of IgG, IgA, IgM was evaluated by indexes of synthesis (Tibbling formula). The blood-brain integrity was estimated by CSF/serum albumin ratio. Increased albumin and immunoglobulins G, A, M levels were demonstrated in first examination and only elevated levels of albumin and immunoglobulin M lasted after four weeks. Albumin level in cerebrospinal fluid and albumin ratio were elevated in both examinations. The serum levels of albumin and immunoglobulins were similar in first and second examination. On the basis these results we conclude that in tested patients blood-brain integrity was disturbed still after four weeks of disease.

[Encephalitis with cerebellar syndrome as rare complication of varicella]. / Rzadkie powiklanie pod postacia zapalenia mózgu z zespolem mózdzkowym w przebiegu ospy wietrznej.

A 17-years old patient with severe encephalitis during chicken-pox is presented. The authors discuss the efficacy of used corticosteroid therapy.