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J Rovensky

Publications and source records attributed to J Rovensky.

At least 37 records · Page 2Linked to original sources
PubMed2003

Cortisol elimination from plasma in premenopausal women with rheumatoid arthritis.

OBJECTIVE: To test the hypothesis that cortisol elimination from plasma can contribute to relatively low cortisol in premenopausal women with rheumatoid arthritis (RA). METHODS: Twelve premenopausal female patients with RA (39.8 (1.8) years) and nine healthy control women matched for age and body mass index (42 (3.3) years) were enrolled in the study. None of the patients had previously been receiving treatment with glucocorticoids. After dexamethasone suppression (2 mg by mouth) the evening before the study, 20 mg of hydrocortisone was given. Blood and saliva samples were drawn six hours after injection of hydrocortisone. Plasma and salivary cortisol were measured. RESULTS: Dexamethasone administration suppressed plasma cortisol concentrations to an almost undetectable level in all subjects, except one with RA. In this subject, a raised concentration of plasma cortisol was verified by repeated analysis despite the fact that cortisol concentration in the saliva sample measured simultaneously was not raised. No significant difference in the disappearance curve of cortisol in plasma or in salivary cortisol levels was found between the patients with RA and the healthy controls. CONCLUSIONS: The profile of disappearance of total cortisol from plasma, and salivary cortisol levels during the elimination phase after its intravenous administration, are unchanged in premenopausal women with RA. Alterations in cortisol clearance are not likely to have a role in cortisol availability in patients with RA.

Adult↗
PubMed2002

Hyperprolactinemia does not influence hypothalamic-pituitary-adrenocortical function during hypoglycemia in women.

Elevated plasma prolactin and mild hypocortisolemia have been observed in patients with rheumatic disorders. This study was designed to assess the potential inhibitory effect of hyperprolactinemia on hypothalamic-pituitary-adrenocortical function. Hypoglycemia was induced by intravenous insulin injection (0.1 IU/kg) in 10 female volunteers of fertile age during their follicular phase twice: 60 min after either domperidone (10 mg orally) or placebo administration. Blood samples were collected from an indwelling catheter inserted into the cubital vein at -60, 0, 30, 45, 60 and 90 min. The concentrations of prolactin, adrenocorticotropic hormone (ACTH), cortisol, epinephrine, norepinephrine and glucose were measured in plasma. Domperidone administration significantly increased plasma prolactin concentrations (71 +/- 11 ng/ml vs. 14 +/- 6 ng/ml; p <0.001), while basal plasma concentrations of ACTH, cortisol, norepinephrine and epinephrine were unaffected. Insulin-induced hypoglycemia resulted in a significant rise in the mean plasma ACTH levels from 10 +/- 1 pg/ml (domperidone) and 11 +/- 1 pg/ml (controls) to 148 +/- 19 pg/ml (domperidone) and 139 +/- 12 pg/ml (controls) at 45 min (p < 0.001), in plasma cortisol from 407 +/- 62 nmol/l (domperidone) and 391 +/- 42 nmol/l (controls) to 925 +/- 60 nmol/l (domperidone) and 810 +/- 52 nmol/l (controls) at 60 min (p < 0.001), and in plasma epinephrine from 40 +/- 26 pg/ml (domperidone) and 16 +/- 3 pg/ml (controls) to 274 +/- 55 pg/ml (domperidone) and 352 +/- 61 pg/ml (controls) at 30 min; (p < 0.001). The significant increase in ACTH, cortisol and epinephrine responses to hypoglycemia was similar in both groups. We observed mild norepinephrine response to hypoglycemia but this was irrespective of the medication. In conclusion, pharmacologically-induced hyperprolactinemia did not induce significant changes of hypothalamic-pituitary-adrenocortical function and did not influence sympathoadrenal activity in healthy young women.

Adrenal Cortex↗
PubMed2001

High-dose intravenous immunoglobulins for lupus nephritis--a salvage immunomodulation.

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease with a great diversity of clinical manifestations which is difficult to manage. IVIGs represent promising immunoregulatory agents with the ability to control SLE without subsequent predisposition to infectious complications. Despite the implied risk of developing renal failure due to IVIG, considerable beneficial effects on lupus nephritis are reported. In this review, the clinical and adverse effects, and mechanism of action, with special emphasis on modulation, of idiotypic network is discussed.

Humans↗
PubMed2001

Alzheimer's disease, inflammation and non-steroidal anti-inflammatory drugs.

Alzheimer's disease (AD) is a degenerative disease of the brain, which causes dementia. The disease is characterised by three main pathogenic factors: senile plaques, neurofibrillary tangles and inflammation. the participation of the local inflammatory reaction is confirmed especially by the results of studies dealing with activated microglia, reactive astrocytes, complement system, cytokines, reactive mediators of oxygen and nitrogen (free radicals), all of which participate significantly in inflammatory processes. These inflammatory markers are locally produced by brain cells, and occur in close proximity of beta-amyloid and tau protein deposits. Moreover, some epidemiologic and pilot clinical studies have proven that long-term administration of anti-inflammatory drugs have a protective effect on the onset of AD. Out of them, non-steroidal anti-inflammatory drugs (NSAIDs) are most extensively investigated medicaments. Despite some contradictory findings, the prevalent majority of these studies prove that long-term application of anti-inflammatory treatment can delay the onset, or at least slow down the progression of AD, namely in people between 65 and 75 years of age. The most appropriate prophylactic effect seems to be achieved by specific inhibitors of cyclooxygenase-2 (COX-2), namely celecoxib and rofecoxib. These preparations protect the gastrointestinal tract better than classical NSAIDs which inhibit both isoenzymes--COX-1 and COX-2. COX-2 is expressed in higher concentrations in the degenerating cells of the brain and this excessive expression can be decreased by selective inhibitors. The latter decrease also the excessive activation of some transcription factors (PPARgama and the nuclear factor kapa-B), which are responsible for the initiation of transcription of a number of pro-inflammatory genes. The selective inhibitors COX-2 can thereby have an anti-inflammatory effect operating on several levels. (Tab. 1, Fig. 1, Ref. 75.)

Alzheimer Disease↗
PubMed2000

Intravenous immunoglobulin treatment of lupus nephritis.

OBJECTIVE: To evaluate the clinical response of treatment-resistant membranous and membranoproliferative lupus nephritis to intravenous immunoglobulin (IVIg). METHODS: Seven lupus nephritis patients who failed to respond to at least prednisone and cyclophosphamide were studied. A kidney biopsy showing either membranous or membranoproliferative glomerulonephritis was available in six patients. They were treated with six courses (patients 1 and 2) or 1 or 2 courses (patients 3 through 7) of high-dose IVIg. For patients 3 through 7, the plasma levels of albumin, total cholesterol, urea, creatinine, dsDNA antibody titers, and daily proteinuria were measured just before the IVIg therapy, immediately on completion, and 6 months later. RESULTS: All seven patients had a beneficial response to IVIg. In patient 1, decrease in proteinuria was evident 2 weeks after IVIg was started, nephrotic syndrome gradually disappeared, and she had no proteinuria in 3 years' follow-up. Decline in proteinuria was evident in patient 2 after the 4th IVIg course, but proteinuria reached the pretreatment level 4 months after the therapy ended. In patients 3 through 7, the mean daily proteinuria before IVIg (5.3 +/- 2.1 g) decreased after 1 or 2 IVIg courses (3.3 +/- 1.4 g), and further decreased when measured 6 months later (2.1 +/- 1.3 g). Similarly, the plasma cholesterol level decreased while the plasma albumin level increased after IVIg. CONCLUSIONS: IVIg might be effective in treatment-resistant membranous or membranoproliferative lupus nephritis. Future studies should concentrate on determining the preferred treatment protocol of IVIg for the various classes of lupus nephritis.

Adolescent↗
PubMed2000

Non-inflammatory enthesopathies of the spine: a diagnostic approach.

Ankylosing vertebral hyperostosis, or hyperostotic disease, is an ossification of the entheses, the regions of insertion of tendons, ligaments or joint capsules into the bone. These ossifications create intervertebral bridges (ossifications of the common anterior, lateral and posterior intervertebral ligaments as well as of the ligamentum flavum), which are responsible for the potential signs of the disease: back and neck pain and stiffness, spinal cord compression at the cervical level and lumbar canal stenosis at the lumbar level. The bony epiphyses are the sites of bony appositions, or enthesophytes, which may compromise joint mobility and increase the risk of secondary osteoarthritis, causing hip and knee disorders in particular. These degenerative joint diseases may eventually necessitate total replacement. In this case, the risk of re-ossification around the prosthesis must be averted by the immediate postoperative prescription of anti-inflammatory medication for 1-2 weeks.

Adult↗
PubMed1999

[Collagen in the treatment of rheumatic diseases--oral tolerance].

The term "oral tolerance" means antigen specific suppression of immune response after oral application of antigen. Primary mechanisms by which oral tolerance is mediated include: deletion, anergy and active cellular suppression. The determining factor in this process is the dose of applied antigen. High doses of antigen develop deletion and anergy of cells while low doses of antigen result in bystander suppression. Recently bystander suppression has attracted attention in the treatment of autoimmune diseases. This process is connected with induction of regulatory T cells of Th2/Th3 phenotypes in gut with characteristic profile of anti-inflammatory cytokines as IL-4, IL-10 and TGF-beta. By means of circulation the lymphocytes enter the affected place and when meeting again with the antigen, they produce the same profile of cytokines which they originally made in the gut. These cytokines then suppress local autoimmune and inflammatory reaction independently of the antigen type. After successful trials of treatment with low doses of orally applied collagen type II in animal models of experimental arthritis, this treatment was also studied in clinical trials in humans with rheumatoid arthritis. Although the results obtained to this date are very promising they can not be considered final. Several questions still need to be solved: identification of responders, determination of character and amount of collagen applied as well as the route of application. Another promising therapeutic approach could be the simultaneous application of collagen and the compounds enhancing the cell response of Th2 or Th3 lymphocytes such as TGF-beta, IL-2, antibodies to IL-12 which can augment the oral tolerance. In clinical praxis the treatment of osteoarthrosis with collagen type I has also been successfully applied. Induction of oral tolerance is new approach in the treatment of rheumatoid arthritis and as each new therapy, it requires refinement. In the future it is expected that an improved study design and a better understanding of the underlying mechanisms of oral tolerance will lead to an increased efficacy of the therapy in humans similar to the effectiveness previously demonstrated in animal models.

Administration, Oral↗
PubMed1988

Effect of human growth hormone and somatomedin on the recovery of sheep red blood cell receptor in peripheral T-lymphocytes.

The effect of growth hormone (GH) and somatomedin (SM) on the recovery of sheep red blood cell (SRBC) receptor in trypsinized human T-lymphocytes was studied either with the use of sera from patients with acromegaly or pituitary dwarfism or after the addition of exogenous GH, SM or thymosin to human sera. It was found that GH does not show any effect on the recovery of SRBC receptor, but it may act through the increase of SM level. It was concluded that the regulation of cellular immunity may be influenced by GH through its stimulatory action on the synthesis and release of somatomedins.

Acromegaly↗
PubMedDate not supplied

Suppression of adjuvant arthritis in rats with chronic bromocriptine treatment does not prevent associated oxidative stress.

We studied the effect of prolactin (PRL) inhibition by bromocriptine (BRC) in the first phase of adjuvant induced arthritis (AA), up to day 11(BRCl-AA), and in the whole time course of AA, up to day 23 (BRC-AA), on the development of the disease in male Lewis rats. On day 24, arthritic rats showed inhibition of PRL secretion, but not PRL mRNA expression in adenopituitaries. BRC treatment suppressed PRL serum levels and PRL mRNA expression in adenopituitaries. In BRC/-AA group PRL levels and PRLmRNA were at the level of rats with AA. Serum corticosterone (CORT) was stimulated by AA from 16.9+/-5.8 to 59.1+/-8.7 ngml(-1), p<0.05, to the same level in BRC-control (BRC-C) and BRC-AA group and further potentiated in BRCI-AA group (148.2+/-33.1 ngml(-1), p<0.05 vs. group with AA). Hind paw swelling was reduced but not completely inhibited in BRC1-AA group and totally prevented in BRC-AA rats as was the core temperature (36.5+/-0.1 degrees C vs. 37.4+/-.0.1 degrees C in AA rats on day 23, p<0.01). Serum concentration of NO-ZNO-3 rose in rats with AA to 28.7+/-2.5 &mgr;mo1L-1 against. 13.9+/-1.9 &mgr;molL(-1) in controls (p<0.01), remained elevated in BRC-AA group and was potentiated in BRC1-AA group (48.2+/-3.5 &mgr;mol(-1), p<0.01 vs. AA or BRC1-AA group) Thiobarbituric acid reactive substances (TBARS) and antioxidant capacity in the spleen were enhanced in rats with AA and to the same extent in BRC-AA or BRC1-AA groups. These results show a discrepancy between the suppression of clinical symptoms and persisting oxidative stress in AA rats after the BRC induced PRL inhibition. The potentiation of nintric oxide (NO-) production after the sudden cessation of PRL inhibition during the disease may promote further joint damage.

Journal Article↗
PubMedDate not supplied

Association between systemic lupus erythematosus and insertion/deletion polymorphism of the angiotensin converting enzyme (ACE) gene.

OBJECTIVE: ACE takes part in the renin-angiotensin and kallikrein-kininogen systems by creating angiotensin-II and inactivating bradykinin. ACE gene insertion/deletion polymorphism is associated with the level of circulating enzymes--subjects with the DD genotype have higher levels of circulating ACE than subjects with the II genotype and show an increased tendency towards impaired vascular function and structure. Patients with systemic lupus erythematosus (SLE) suffer from differentially expressed vascular pathology. We attempted to determine whether the type of ACE polymorphism could contribute to this pathology. METHODS: 101 SLE patients fulfilling the ACR criteria were investigated. The I/D polymorphism was ascertained by PCR, followed by electrophoresis of the amplified fragments and UV visualization. RESULTS: The frequency of the D allele was higher in the SLE group (0.623) than in the controls (0.520) (chi 2 test, p < 0.025). The distribution of the ACE genotype in SLE group was different from that in the control group (p < 0.05). An association between the DD genotype and visceral damage (p < 0.006) was observed. CONCLUSION: Our results suggest that in the multifactorially determined vascular pathology of SLE, changes associated with I/D polymorphism could influence vessel wall inflammation (monocyte adhesion and activation with cytokine release, T-lymphocyte metabolism), a tendency towards vascular impairment (neointimal proliferation, vasospasm, platelet activation, myocyte proliferation) and lead to the subsequent ischemia. The ACE gene could serve as the visceral damage indicator in SLE.

Adolescent↗
PubMedDate not supplied

Cytotoxic T lymphocyte antigen 4 (CTLA-4) dimorphism in patients with systemic lupus erythematosus.

OBJECTIVE: Genetic susceptibility to systemic lupus erythematosus (SLE) is conferred not only by various genes within the major histocompatibility complex (MHC) region, but also by several other non-MHC linked genes. The negatively signalling molecule CTLA-4 is involved in establishing and maintaining of peripheral T cell tolerance, which controls T cell activation and reactivity. Its attenuating action helps to prevent an inappropriate initiation of T cell responses to self antigens and to terminate ongoing T cell responses. We tested if there was an association between CTLA-4 and SLE, a disease with B and T cell hyperreactivity and impaired peripheral T cell tolerance. METHODS: Using the polymerase chain reaction--restriction fragment length polymorphism method with Bbv I digestion, we assessed an exon 1 transition dimorphism (49 A/G) of the CTLA-4 gene in 102 SLE patients and in 76 healthy controls. RESULTS: The distribution of CTLA-4 exon 1 genotypes in the SLE group was significantly different from that in the controls (chi 2 = 6.178, p < 0.05). 17.6% of the SLE patients were G/G homozygotes compared to 5.3% of the controls; 36.3% were A/G heterozygotes vs 40.8% of controls; and 46.1% were A/A homozygotes vs 53.9% of the controls. The frequency of the G allele was significantly higher in SLE patients (35.8%) than in controls (25.7%; chi 2 = 4.142, p = 0.042). CONCLUSION: Our results indicate that the non-MHC linked CTLA-4 gene could confer susceptibility in SLE, as it does in various other autoimmune diseases (Hashimoto thyroiditis, Graves' disease, IDDM).

Abatacept↗
PubMedDate not supplied

Evidence for hyaluronan production in the air pouch model in rats.

OBJECTIVE: The aim of our work was to investigate the presence of hyaluronan (HA) in the rat air pouch and its behaviour in response to inflammatory stimuli. METHODS: HA levels (by a microplate assay) and the leucocyte count were determined in the fluid obtained from air pouches in which acute or subacute inflammation had been induced by the injection of monosodium urate crystals (MSU) or high density polyethylene (HDPE) debris respectively and in relative controls. RESULTS: In control pouches of both groups, remarkable levels of HA were found; these levels were higher in the very first hours (2475 and 1850 micrograms/l at 6 hrs) and then gradually decreased. In pouches injected with MSU, HA moderately increased (p < 0.001) after 6 hrs, reached a peak after 12 hrs (p < 0.001) and began to taper at 24 hrs (p < 0.001). The leucocyte count was also increased at 6 hrs (p < 0.001), became higher at 12 hrs (p < 0.001) and tapered at 24 hrs (p < 0.001). In the HDPE pouches, HA levels were significantly reduced with respect to controls after 6 hours (p < 0.001), increasing later (p < 0.001) to reach a peak at 24 hrs (p < 0.001), and returning to the original levels, or even below, in the following 72 hours. CONCLUSIONS: These data confirm that the pouch lining produces fair amounts of HA and provide evidence that, in this system, HA levels seem to be influenced by the degree of inflammation even if with variable behaviour in relation to the different characteristics and phases of phlogosis. The present data suggest that the air pouch is a useful experimental model for studies on HA metabolism in either acute or chronic inflammation.

Air↗
PubMedDate not supplied

CC chemokine receptor 5 and interleukin-1 receptor antagonist gene polymorphisms in patients with primary Sjögren's syndrome.

OBJECTIVE: Interleukin-1 receptor antagonist (IL-1Ra) and also mononuclear cell-attractant chemokines CCL3, CCL4 and CCL5 have been implicated in the immunopathogenesis of primary Sjögren syndrome (pSS). Both the gene coding for receptor CCR5 binding the aforementioned CCL ligands and the gene for IL-1Ra are polymorphic. We have therefore in a case control study assessed the putative role of these "candidate" polymorphic genes in the inflammatory process in Sjögren syndrome. METHODS: DNA was obtained from 39 unrelated patients with primary Sjögren's syndrome and 76 unrelated healthy controls; all subjects were Caucasians of Slovak origin. CCR5 delta 32 and IL-1Ra VNTR polymorphisms were genotyped by PCR-SSP. RESULTS: The frequencies of CCR5 delta 32 in patients with pSS were different from that in control subjects: there was an apparent decrease of the mutant allele in the patient group. CCR5 delta 32/CCR5 heterozygosity was associated with a reduced relative risk of pSS (OR 0.35, p = 0.043). There was no difference in the distribution of the alleles of the IL-1Ra VNTR polymorphism between the groups of pSS patients and control subjects. CONCLUSION: In this population of patients with Sjögren's syndrome, the frequency of CCR5 delta 32/CCR5 genotype is significantly decreased. The data suggests that carrier status for the CCR5 delta 32 allele may contribute to protection from the development of primary Sjögren's syndrome. In contrast, IL-1Ra VNTR polymorphism does not confer susceptibility to primary Sjögren's syndrome in Slovak Caucasians.

Alleles↗