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Biomedical subjects

V Lackovic

Publications and source records attributed to V Lackovic.

At least 19 recordsLinked to original sources

Regional hemodynamics after chronic nitric oxide inhibition in spontaneously hypertensive rats.

BACKGROUND: Inhibition of nitric oxide (NO) synthase by L-arginine analogs is associated with elevation of blood pressure in rats. Because endothelium-dependent vasomotion in different vascular beds is not homogenous, the aim of this study was to characterize and compare regional hemodynamic responses in carotid, femoral, and renal vascular beds after chronic NO inhibition in spontaneously hypertensive rats. The possible role of circulating endothelin and renin angiotensin systems in mediating the effects of chronic NO inhibition was also studied. METHODS: Systemic and regional hemodynamics, left ventricular mass, plasma renin activity, and plasma endothelin-1 were determined in control and Nomega-nitro-Larginine methyl ester (L-NAME)-treated (10 mg/kg/day, 4 weeks) spontaneously hypertensive rats. RESULTS: L-NAME treatment increased arterial pressure and total peripheral and regional vascular resistance and decreased cardiac output, stroke volume, and regional blood flow. An increase in blood flow ratio and a decrease in vascular resistance ratio between carotid and renal as well as femoral and renal vascular beds in rats treated with L-NAME was found. Blood flow and vascular resistance ratios between femoral and carotid vascular beds remained unchanged. L-NAME increased plasma renin activity and left ventricular weight/body weight ratio, whereas plasma endothelin-1 was not modified. CONCLUSIONS: The results of this study showed that the renal circulation seemed to be more sensitive to the effects of chronic NO inhibition than carotid and femoral vascular beds. Simultaneous activation of the renin angiotensin system may further potentiate cardiovascular effects of chronic NO inhibition. No evidence that circulating endothelin-1 plays a role in this model of hypertension was found.

Angiotensins↗

Plasma cytokine concentration and the cytokine producing ability of whole blood cell cultures from healthy females with pharmacologically induced hyperprolactinemia.

We investigated the in vitro effect of domperidone-induced hyperprolactinemia on plasma cytokine concentration and blood leukocyte cytokine production in healthy female volunteers. No changes were found in the plasma concentration of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, IL-10, IL-6 and IL-13 during hyperprolactinemia when compared with control values. Using unseparated blood leukocytes, we found that the spontaneous production of IL-6 (4-8 h) and transforming growth factor (TGF)-beta 1 (2-4 h) was significantly decreased and that the in vitro stimulated production of IFN-gamma (2-8 h) and TNF (4 h) was significantly increased compared with control. Our data concerning the increased IFN-gamma and TNF producing capacity of unseparated leukocytes during pharmacologically induced hyperprolactinemia strongly support the possibility that the lymphocyte production of these cytokines can be rapidly amplified by prolactin via a priming mechanism.

Adult↗

The effects of long-term low-protein intake on gastrin cells of the rat antral mucosa during adulthood.

The effect of experimental protein malnutrition on gastrin producing cells in the antral part of the stomach was studied in male Wistar rats. Isoenergetic diets containing 25% (C-25) or 6% (PD-6) were given in isocaloric amounts during a 4-month experiment. All rats were offered drinking water ad libitum. The results showed that the long-term protein diet did not produce changes in the gastrin cell number. At the ultrastructural level G cells exhibited a decreased size of the nucleus. They were found to have an increased total granule volume density but the volume density of dense-cored granules was lower. The serum gastrin levels were significantly lowered by feeding the low protein diet. These changes are compatible with decreased functional activity of G cells under long-term protein deprivation.

Animals↗

Effect of domperidone-induced hyperprolactinemia on selected immune parameters in healthy women.

Domperidone, anti-emetic drug, given to healthy female volunteers, induced an elevation of plasma prolactin (PRL) concentration with the peak in 1-4 h. The release of prolactin had a transient stimulating effect on theophylline sensitive T lymphocytes and on concanavalin A induced mitogenic activity, suggesting an enhanced activity of T suppressor lymphocytes. The relative number of CD4+ lymphocytes decreased markedly one hour after domperidone administration and returned to normal values within 2 h (that means 3 h after taking the drug). The number of lymphocytes positive for dipeptidyl peptidase IV exhibited similar transient increase and normalization of activity. No change was observed in the number of CD8+ lymphocytes. The production of interferon by leukocytes treated with Newcastle disease virus was found to be significantly increased 2 h after domperidone administration. The results suggest that prolactin can selectively stimulate some functions of cellular immunity as well as the release of cytokines (IFN). The present study may contribute to the understanding of the role of the immune system in endogenous hyperprolactinemia.

Adolescent↗

A comparison of regulatory cells in spinal fluid and blood in patients with multiple sclerosis and other neurologic diseases.

Multiple sclerosis is a disease in which immune abnormalities are present both in the CNS and peripheral blood. Whether these changes are primary or secondary to the disease process is not known. We tested T-cell clones derived from activated lymphocytes in the blood and CSF of MS patients and controls for their capacity to regulate T-cell responses to alloantigens. A wide spectrum of regulatory functions were observed, ranging from marked enhancement to almost complete suppression. Clones from different patient populations and anatomic sites were equivalent in their regulatory functions with the net effect of clones in each compartment being suppression. However, certain clones from CSF and peripheral blood had the capacity to stimulate autologous T cells. Percentages of such clones in the peripheral blood of MS patients were significantly higher than in controls, while percentages in MS and other neurologic diseases (OND) CSF were equivalent. Our data suggest that (1) functional suppressor cells are not lost from the blood or CSF or MS and OND patients, (2) lymphocytes that have entered the CNS in patients with MS and other CNS diseases have equivalent regulatory functions, (3) MS may be an illness in which peripheral immunologic events are important in perpetuating the disease process, and (4) responses to autologous antigens may also play a role in this perpetuation.

Adult↗

[Immunobiologic properties of lactobacilli].

The authors investigated in experiments on mice immunobiological properties of selected strains of lactobacilli (Lbc. acidophilus, Lbc. casei and Lbc. delbruecki). Their immunostimulating action was evaluated from the migrating capacity of lymphocytes into the interepithelial spaces and lamina propria mucosae of the gut. The most marked changes were observed in the group of animals to whom Lbc. acidophilus and Lbc. casei was administered for two weeks by a gastric tube. The protective properties of lactobacilli on the course and development of model infections (virus of encephalomyocarditis) was greatest in mice given Lbc. casei and Lbc. acidophilus by the intraperitoneal route four days before infection. At the end of the two-week period in the Lbc. casei group 66% mice survived and in the Lbc. acidophilus group 34%. The ability of lactobacilli to influence the interferon producing activity was investigated in vitro on a model of peritoneal cells obtained from premedicated mice. The lactobacilli strains themselves did not have interferon inducing properties. However, when the interferon producing capacity of peritoneal cells was assessed after administration of the viral inducer (virus of Newcastle disease) the capacity was much higher, when compared with controls.

Adjuvants, Immunologic↗

Blood-brain barrier permeability changes during acute allergic encephalomyelitis induced in the guinea pig.

Blood-brain barrier permeability to homologous serum 125I-IgG and to D-[3H]mannitol was studied by means of the brain vascular perfusion method in guinea pigs with experimental allergic encephalomyelitis (EAE). EAE was induced with homologous myelin basic protein (MBP) after pretreatment with foreign protein and muramyl dipeptide (MDP). The results suggest a significant comparable increase in IgG blood-to-brain clearance in the parietal cortex, hippocampus, and caudate nucleus, during vascular perfusion of the brains of animals, after 7 and 20 days of EAE. On the other hand, unidirectional transfer of mannitol in the same period of EAE was markedly augmented only in the hippocampus, but no significant changes in the parietal cortex or caudate nucleus were observed. Cerebrospinal fluid (CSF)/serum ratios for IgG and albumin were both significantly increased, suggesting an increase in blood-CSF barrier permeability, but more for albumin than for IgG. The results were confirmed by immunohistochemical determination of the IgG deposits in the brains of EAE animals, during vascular perfusion with unlabeled homologous IgG. An important role of the blood-brain barrier for the central nervous system immunoglobulin homeostasis during EAE is suggested.

Animals↗

Human acid- and thermolabile alpha-interferon-like substance: selective reactivity with a monoclonal antibody.

An acid- and thermolabile alpha-interferon-like substance, designated AL-IFN-alpha, has been found in non-processed normal human leukocyte IFN preparations as well as sera from patients with autoimmune or other chronic diseases. Little is known about origin, production and biological activity of these IFN activities. Monoclonal antibodies were obtained which proved highly selective in neutralizing AL-IFN-alpha in both anti-proliferative and antiviral tests. While the monoclonal antibodies were strict specific, polyclonal antibodies against various interferons showed less specificity in these tests. The results suggest that AL-IFN-alpha represents an antigenically distinct IFN-alpha subtype or, alternatively, a new lymphokine with antiproliferative and antiviral activity.

Acids↗

Abnormal macrophages and NK cell cytotoxicity in human systemic lupus erythematosus and the role of interferon and serum factors.

Macrophage (MO) and natural killer (NK) cell mediated cytotoxicity to K562 target cells were strikingly decreased in patients with systemic lupus erythematosus (SLE). SLE NK cells failed to release soluble factor(s) for lysing the targets. IFN-induced enhancement of both types of cytotoxicity was impaired. NK cells from healthy subjects kept their activity in culture with or without IFN for more than six days whereas SLE NK cell activity declined to zero at day 3. So, the increased IFN level of many SLE patients and a possible prior IFN priming effect seemed unrelated to the insensitivity to exogenous IFN in vitro. Inhibition factor(s) of SLE serum suppressed NK cytotoxicity in the presence of IFN whereas IFN sensitivity of MO remained unaffected indicating the complex regulation by serum components of immune reactions.

Chromium Radioisotopes↗

Monoclonal antibodies neutralizing human leukocyte acid- and thermolabile interferon alpha.

Using a high titred human leukocyte IFN alpha preparation which contained both acid- and thermolabile (AL-IFN alpha) and acid- and thermostable IFN alpha species in 9:1 proportion for immunization of BALB/c mice, five hybridomas secreting monoclonal antibodies that reacted with AL-IFN alpha were obtained. In antiviral and antiproliferative tests on HL-60 cells, their products showed high degree of specificity for AL-IFN alpha. The results suggest that both the "normal" leukocyte AL-IFN alpha and the IFN alpha found in sera of autoimmune and other chronic patients might belong to the same subtype of IFN alpha.

Animals↗

Activation of NK cells in subjects exposed to mild hyper- or hypothermic load.

The effect of mild hyper- and hypothermic stress on release of selected hormones (somatotropin, noradrenaline, etc.), interferon (IFN), and activity of NK cells in the blood was examined in groups of young males during a 30 min exposure to 39 degrees C and 4 degrees C. A quick release of somatotropin was registered in 44% of examinees in the hyperthermic group, while the persons exposed to 4 degrees C reacted with a release of noradrenaline only. Concurrently, an elevation of NK cell activity was observed both in the subgroup releasing somatotropin after hyperthermic stress and in the group exposed to cold. Since these forms of mild stress did not lead to an appearance of IFN in the serum, the possibility of an NK cell activating effect of somatotropin and/or the adrenal hormones was tested. While the adrenal hormones stimulated the NK cell activity in vitro, no support for a similar role for somatotropin was found.

Adult↗

Combined effects of interferon and mutagens on survival of mouse L929 cells.

We studied the effect of mouse interferon (IFN) alpha/beta on the sensitivity of L929 cells to cytotoxic activity of ultraviolet (UV) irradiation or ethyl methanesulfonate (EMS) administration. Exposure of L929 cells to IFN for 48 h before mutagen treatment markedly enhanced their sensitivity to UV, but only slightly to EMS. Incubation of L929 cells after UV-irradiation for 24 h in the presence of low concentrations of IFN (15 units/ml) increased the cellular recovery, while with graded concentrations of IFN the protective activity was inhibited (60 units/ml) and after 250 units/ml the ability of IFN treated cells to recover was found to decrease. Incubation of cells after EMS treatment for 24 h with low (15 units/ml) or moderate (60 units/ml) IFN concentrations markedly reduced the cellular recovery. It has been shown that the extent and the direction of IFN activity on cellular sensitivity to mutagens was influenced by the type of mutagen, IFN-concentration and length of its action on the cell and upon application of IFN before or after mutagen treatment.

Cell Survival↗

Early intrathecal production of specific IgM and IgG antibodies and alpha-interferon in herpes simplex virus encephalitis.

A complex approach was used in order to establish non-invasively the aetiology in three cases of encephalitis presumptively caused by herpes simplex virus (HSV). As indicative of brain HSV infection was considered the lowered serum to cerebrospinal fluid specific antibody ratio, which also assessed the humoral immune response within the CNS. For this purpose, during ongoing brain tissue infection, the early intrathecal (ITH) production of IgG and IgM antibodies was analysed by a differential enzyme-linked immunosorbent assay (ELISA) along with changing levels of complement-fixing (CF) antibodies in the serum and cerebrospinal fluid (CSF). Antiviral antibody (AA) response was markedly preceded by the appearance of alpha-interferon (IFN) in the serum and CSF. From the CNS biopsy and autopsy specimens one HSV-1 and one HSV-2 strain were recovered.

Adolescent↗

Clinical and immunological characterization of systemic lupus erythematosus in patients with circulating interferon and migration inhibitory factor.

The simultaneous occurrence of interferon and migration inhibitory factor was found in sera from 9 patients with systemic lupus erythematosus (SLE). Their clinical picture was characterized by a moderate course of the disease. In 7 patients the inflammatory tendoarticular manifestations were accentuated. Glomerulonephritis was found only in 3 patients and was successfully suppressed by immunosuppressive therapy. In the peripheral blood of most of these patients, normal or moderately increased levels of active E-rosettes were found. Therefore we consider these SLE patients as a group with characteristic signs of activated cell-mediated immunity (lymphokine release, active E-rosettes). Although the reason for this activation remains unknown, we suppose that some concomitant bacterial infection, perhaps mycobacterial, may contribute to this immunological phenomenon.

Adult↗