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Biomedical subjects

M Dimitrijević

Publications and source records attributed to M Dimitrijević.

At least 19 recordsLinked to original sources
PubMed2000

Modulation of humoral immune responses in the rat by centrally applied Met-Enk and opioid receptor antagonists: functional interactions of brain OP1, OP2 and OP3 receptors.

We have previously demonstrated that central application of leucine-enkephalin (Leu-Enk) elicits potentiation and suppression of humoral immune responses through OP(1) (delta) and OP(2) (kappa) receptors, respectively. Interestingly, both effects were found to be additionally dependent on OP(3) (mu) receptor function. In the present study, we have further investigated whether opioid receptor interactions underlie the immunomodulatory effects of endogenous opioids as well as exogenously applied methionine-enkephalin (Met-Enk). For that purpose, the plaque-forming cell (PFC) response was determined in rats injected intracerebroventricularly (i.c.v.) with opioid receptor-selective antagonists and Met-Enk. Application of the OP(1) antagonist ICI 174864, but not naltrindole, resulted in suppression of the PFC response. In contrast, i.c.v. injection of the OP(2) selective antagonist nor-binaltorphimine (nor-BNI) significantly potentiated the PFC response. Both effects, presumably mediated by endogenous opioid peptides, were antagonized by the OP(3) receptor antagonist beta-funaltrexamine (beta-FNA) at a dose that was devoid of immunomodulatory activity. The immunopotentiation of the PFC response induced by Met-Enk was reversed by OP(1) receptor antagonists, naltrindole and ICI 174864, but not by beta-FNA or nor-BNI. On the basis of these and previous findings, it may be concluded that central OP(3) receptors are permissive for the central immunomodulatory action of endogenous opioid peptides and Leu-Enk. In contrast, the central immunoenhancing effect of Met-Enk appears to be mediated through OP(3)-independent OP(1) receptors.

Adjuvants, Immunologic↗
PubMed2000

A monoclonal antibody to the rat Crry/p65 antigen, a complement regulatory membrane protein, stimulates adhesion and proliferation of thymocytes.

A murine monoclonal antibody (mAb), 3F10, was produced by fusion of spleen cells obtained from mice immunized with a rat cortical thymic epithelial cell line (R-TNC.1) stimulated with interferon-gamma and P3X myeloma cells. 3F10 recognized an antigen expressed both on thymocytes and non-lymphoid cells in the thymus. Flow cytometry showed that 3F10 stained more than 98% thymocytes and 90% R-TNC.1 cells. Immunoprecipitation and Western blot studies demonstrated that 3F10 reacted with molecules of 55000 and 65000 MW from both thymocyte and R-TNC.1 cell lysates. 3F10 recognized the same antigen on Chinese hamster ovary cells transfected with rat Crry as did 5I2 mAb, confirming the specificity of 3F10 mAb for the rat homologue of mouse Crry/p65, a membrane-bound complement regulatory protein. 3F10 mAb induced homotypic aggregation of thymocytes and exhibited an additive effect on the aggregation evoked by phorbol myristate acetate. The aggregation was dependent on active cell metabolism, intact cytoskeleton, divalent cations and activation of protein phosphatases 1 and 2A (as assessed by use of okadaic acid). In contrast, H-7, HA1004 and genistein partially inhibited, whereas staurosporine potentiated the aggregation of thymocytes triggered by 3F10. 3F10 mAb also stimulated binding of thymocytes to the R-TNC.1 line. Both homotypic and heterotypic adhesive interactions are mediated by leucocyte function-associated antigen-1 (LFA-1). In addition, 3F10 stimulated proliferation of thymocytes induced by suboptimal concentrations of concanavalin A. These data suggest that rat Crry/p65 might be involved in the regulation of both cell adhesion and activation of thymocytes. This is a novel, non-complement-dependent function of Crry/p65.

Animals↗
PubMed2000

Peripheral effects of methionine-enkephalin on inflammatory reactions and behavior in the rat.

Methionine-enkephalin (Met-Enk) induces notable alterations in immune and central nervous system functions. The present study was conducted in order to compare peripheral and central effects of Met-Enk on nonspecific immunity, open field behavior and pain perception in the rat. The results showed that 0.2 mg/kg of Met-Enk given intraperitoneally (i.p.) increased concanavalin A (Con-A)-induced paw edema and enhanced basal and phorbol myristate acetate (PMA)-stimulated H(2)O(2) production of peritoneal macrophages. Met-Enk-induced immunopotentiation was antagonized by anti-Met-Enk antibodies (anti-Met-Enk-Ig) and quaternary naltrexone (qNtx). Met-Enk injected i.p. produced an increase of horizontal and vertical locomotor activity in the open field that was reversed by i. p. administration of anti-Met-Enk-Ig and qNtx. The dose of 0.2 mg/kg of Met-Enk applied i.p. did not affect the number of writhes in the test of analgesia. Intracerebroventricular (i.c.v.) injection of Met-Enk, given in a dose that was previously shown to be immunostimulatory, enhanced only basal H(2)O(2) production of peritoneal macrophages, and anti-Met-Enk-Ig antagonized this effect. Besides, i.c.v. treatment with anti-Met-Enk-Ig increased and decreased H(2)O(2) production of peritoneal macrophages under basal and stimulated conditions, respectively. Met-Enk and anti-Met-Enk-Ig injected i.c.v. did not influence activity in the open field and pain sensitivity. Thus, the i.c.v. dose of Met-Enk that was sufficient to modulate immune functions did not influence behavior. It may be concluded that Met-Enk modulated nonspecific immune responses and open field behavior by peripheral mechanisms.

Animals↗
PubMed1997

Stress-induced rise in serum anti-brain autoantibody levels in the rat.

Sera from Wistar rats subjected to different stress procedures were tested by ELISA for the presence of autoantibodies with specificity for neuron-specific enolase (NSE) and S100 protein that are preferentially localized in neurons and glia, respectively. Autoantibodies were present in sera of animals before exposure to stress, and raised with age. Anti-NSE and anti-S100 autoantibody levels were increased one day after termination of restraint (2 hours daily, 10 days) and electric tail shock (80 shocks daily, 19 days), and in fifth and tenth week of overcrowding stress. Differences between stressed and control animals were not present one month following restraint and electric tail shock and in twentieth week of overcrowding.

Animals↗
PubMed1995

Experimental allergic encephalomyelitis in adult DA rats subjected to neonatal handling or gentling.

The present study investigated the effect of daily handling and gentling between postnatal days 1 and 28 on experimental allergic encephalomyelitis (EAE) in 8-week old DA rats. Handling consisted of removing pups from the mother, and placing them in the novel cage for 15 min. The gentling procedure included handling accompanied by 3 min of dorsal tactile stimulation before returning the pups to the nest cage. Adult rats of both sexes handled in infancy showed increased susceptibility to EAE, as revealed by higher incidence of the disease, and more severe clinical signs. Anti-myelin basic protein (MBP) autoantibodies were increased in handled males, and decreased in handled females, compared to controls. Gentling induced aggravation of clinical signs and histopathological lesions of EAE in males, while in gentled females suppression was observed. These results indicated that both neonatal handling and gentling aggravated EAE induced in adult male rats. In female rats handling exacerbated, and gentling suppressed clinical EAE. The overall effect of neonatal manipulations was more pronounced in males. Furthermore, in mothers separated from their offspring due to handling and gentling, and immunized for EAE at day 28 postpartum, earlier appearance of clinical signs, and increased frequency of relapses compared to control dams was recorded.

Animals↗
PubMed1995

Maternal deprivation and early weaning modulate experimental allergic encephalomyelitis in the rat.

The present experiment deals with the effect of maternal deprivation (MD) and early weaning (EW) on the development and course of experimental allergic encephalomyelitis (EAE) in Dark August (DA) rats. Five litters (five to nine pups per liter) were subjected to MD (4 h daily) from Day 1 until Day 28. EW rats were weaned on Day 15 (EW-15, five litters) or Day 21 (EW-21, four litters). Control rats and MD rats were weaned on Day 28. At the age of 8 weeks, rats were immunized with guinea pig spinal cord in complete Freund's adjuvant and clinical signs of EAE were recorded daily. On Day 18 after immunization, rats were bled and sacrificed. Brain and spinal cord were examined histologically for EAE lesions. Serum anti-rat myelin basic protein (MBP) antibodies were detected by ELISA. MD female rats exhibited suppression of neurological and histological signs of EAE in comparison with control rats. MD and control females showed elevated anti-MBP antibody level compared to MD and control males. EW-15 female rats demonstrated potentiation of neurological signs of EAE compared to control females. EW-21 females developed more severe clinical signs and histological lesions compared to control females. These results show that neonatal experiences, such as maternal deprivation and early weaning, influence the development of EAE in adult DA rats.

Age Factors↗
PubMed1995

Suppression of experimental allergic encephalomyelitis in offspring of DA and Wistar rats following immunization of mother with encephalitogen.

Immunization of female rats with encephalitogen before gestation, during gestation, and during lactation differentially decreased susceptibility to experimental allergic encephalomyelitis (EAE) in their offspring. The most pronounced suppression, revealed by lowered incidence and weaker clinical signs of the disease, was observed in offspring of mothers immunized before gestation and during lactation in both Dark August (EAE-susceptible), and Wistar (EAE-relatively resistant) rat strains. Induction of EAE in mothers during pregnancy only delayed the onset of the disease in DA progeny. The overall effect on EAE in offspring did not depend on the disease intensity in mothers. Our results suggest that anti-myelin basic protein (MBP) antibodies passively transferred from mothers are not responsible for the observed protection in offspring.

Animals↗
PubMed1995

Effect of Met-enkephalin and opioid antagonists on rat macrophages.

Effects of Met-enkephalin (Met-ENK) and opioid antagonists on H2O2 release by peritoneal macrophages from DA and AO rats were investigated. Met-ENK increased and decreased H2O2 production by macrophages of DA and AO rats, respectively. These effects were antagonized by low, but not high, concentrations of naloxone and ICI 174864. High concentrations of both antagonists directly modulated H2O2 release and retained the strain-related differences seen with Met-ENK. The results showed direct, strain- and dose-dependent, effects of Met-ENK, naloxone, and ICI 174864 on rat macrophage function.

Animals↗
PubMed1994

Neonatal sound stress and development of experimental allergic encephalomyelitis in Lewis and DA rats.

This experiment deals with the effect of neonatal sound stress on the susceptibility of rats in adult life to the induction of experimental allergic encephalomyelitis (EAE). Two inbred strains of rats, Lewis and DA, highly susceptible to EAE were used. On postnatal days 15, 18 and 21, animals of both sexes were sound stressed in a sound attenuated chamber (90dB, 60 rings/5 sec during 1 h, on a variable interval schedule) in the presence or absence of the mother. Experimental groups were as follows: (a) pups stressed without the mother (SP); (b) pups stressed in the presence of the mother (SPM); (c) control nonstressed pups separated from the mother (CP), and (d) control nonstressed pups undisturbed in their nest cages (CPM). Rats were weaned on postnatal day 28. At the age of 8 weeks, all groups were immunized with guinea pig spinal cord in complete Freund's adjuvant. Signs of EAE were recorded daily until the day 20 after immunization when animals were bled and sacrificed. Serial sections of cerebrum, cerebellum and spinal cord were examined histologically for the presence of mononuclear cell infiltrates. Anti-myelin basic protein (MBP) antibodies were detected in serum samples using ELISA technique. Stressed Lewis rats (groups SP and SPM) compared to control groups CP and CPM, developed more severe EAE as revealed by a higher aggregate clinical score, more pronounced histological lesions and increased production of anti-MBP antibodies. The presence of the mother during stress session (group SPM) prolonged the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effect of early experience on behavior and immune response in the rat.

The effect of maternal deprivation (MD) and preweaning handling on open field (OF) behavior, body and organ weights (spleen, thymus, and adrenals), and humoral immune response (plaque-forming cell response and antibody production) in adult male and female Wistar rats was studied. Maternal deprivation took place either for 28 postnatal days (2 h/day), or on days 15, 18, and 21 (2 h/day), whereas handling was performed daily during 28 postnatal days for 3 min. Sex differences were found both in behavior and immune response. The MD rats showed ambulatory hyperactivity in OF tests, females being more active than males, and a marked suppression of the PFC response. Handled rat's behavior was distinguishable from MD rats by an increased curiosity. Female handled rats were more active in the OF and their antibody production was higher. Male handled rats showed higher defecation scores and lower plaque-forming cell response. These results present evidence for a deprivation syndrome and immunosuppressive behavior in MD rats. Several mechanisms that may account for these immunobehavioral results are outlined.

Animals↗
PubMed1991

Stress-induced resistance to anaphylactic shock.

There have been many reports of the immunomodulatory effects of stress, but the influence of stress on anaphylaxis has been given little attention till now. In this study we investigated the influence of tail-shock stress on the course of anaphylactic shock (AS) in the rat. For this purpose, rats were sensitized to ovalbumin and subjected to stress procedure before the induction of AS. In the first series of experiments we used chronic (4 day) stress consisted of 80 inescapable tail shocks delivered at the same time each day. Anaphylactic shock was induced 24 hours later by intraperitoneal injection of 3 mg of ovalbumin. Results showed that stressed rats exhibited lower intensity of three investigated parameters of AS: clinical signs, hematocrit values, and drop of rectal temperature. In order to investigate whether acute stress procedure could also influence course of AS, rats were given various shock doses of ovalbumin immediately after the end of acute (1 day) tail-shock stress. Anti-anaphylactic effect of acute stress was demonstrated to be dose-dependent: the greatest protective effect was in animals that received the highest shocking dose of ovalbumin. Finally, we examined the duration of protective effect of acute inescapable tail shocks on AS, and these results showed that observed anti-AS phenomenon disappears 72 hours after the end of acute stress session.

Anaphylaxis↗
PubMed1991

Stress-induced suppression of experimental allergic encephalomyelitis in the rat.

Numerous experiments have demonstrated that physical stress can alter immunological parameters. However, little attention has been paid to the interrelationship between stress and autoimmune processes. The present study was designed to determine the influence of electric shock and sound stress on the development of experimental allergic encephalomyelitis (EAE). Ten-week-old male DA rats highly susceptible to EAE were used. Rats were subjected to the stress procedure during 19 days either before or after immunization with intradermal injection of 0.1 ml of an emulsion containing guinea pig spinal cord (20 mg/rat) in an equal volume of complete Freund's adjuvant (CFA). In addition, rats received subcutaneous injection of Bordetella pertussis in the dorsum of the same foot. Electric stress procedure consisted of 80 inescapable, unpredictable tail shocks (5 s, 1 mA) delivered at the same time each day. Sound stress procedure consisted of exposure of rats to a 90 dB fire alarm bell which rings 60 times for 5 s during one hour, at the same time of the day. Rats were observed daily for clinical signs of EAE and survived animals were sacrificed on day 20 after immunization. The brain and spinal cord sections were examined histologically for mononuclear cell infiltrates characteristics for EAE. The results clearly indicate that inescapable tail shocks suppressed the appearance and development of EAE when rats were subjected to stress procedure during 19 days after immunization, but not when rats were stressed during 19 day before the induction of EAE. On the other hand, in rats exposed to sound stress there was only delay in the onset of the disease.

Animals↗
PubMed1989

[Rupture of the spleen and the surgical approach].

In introduction, the authors present, theoretical considerations about divide of spleen injury, and give appropriate statistical data. In their material consisted of 25 traumatically ruptured spleens during period 1974-1988, they deal, among other questions, with necessity of drainage after splenectomy. As for operative procedure, they point out splenectomy, but also mention other surgical treatments that they are not familiar with. In conclusions they insist on early and precise diagnosis (especially in multi injured patients) and emphasize close relationship between drainage and local intraoperative finding.

Humans↗
PubMed1989

[Drainage of the pericystic cavity in echinococcosis of the liver].

The authors emphasize that echinococcosis is cosmopolitan parasitosis and liver is the most often target organ. The most common complications are summarized. At any slightest doubt of the liver infection, the authors recommend modern diagnostic tools (ultrasonography CT) in liver examination. They analyze their lo years experience (20 hepatal). The conclusion is that basic therapeutic procedure is removing of pericyst content with hydatid membrane and residual cavity is treated later. The authors accept updated biac of liver echinococcosis treatment (radical removing of pericyst performing typical or atypical resection, or total lobectomy in case of lobar destruction). However they point out that drainage operations (marsupialization, external drainage with rubber drain, irrigation-aspiration drainage, T-drainage and internal drainage omentopeksia, anastomosis of the cavity with jejunal lumen) still have their place and value in Surgery.

Drainage↗