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Biomedical subjects

D Marić

Publications and source records attributed to D Marić.

At least 19 recordsLinked to original sources
PubMed1991

Enkephalin-induced stimulation of humoral and cellular immune reactions in aged rats.

Twenty-month-old Wistar rats received intraperitoneal injections of the opioid pentapeptide, methionine-enkephalin (Met-Enk) in periods before and after immunization with cellular and soluble antigens. Animals were treated with 0.2 mg of Met-Enk/kg b.w., a dose previously found to increase immune capacity in young adult rats. Saline-treated 20-month-old, and Met-Enk-treated rats and saline-treated 8-week-old controls were set up for each experimental group. Immune performance was evaluated by plaque-forming cell response, antibody production and various immunoinflammatory reactions. At autopsy, thymus and spleen were weighed and processed for histological examination. The results showed that 0.2 mg dose of Met-Enk produced significant enhancement of both humoral and cellular immune responses in senescent rats. Methionine-enkephalin treatment also induced a significant increase in thymus and spleen weights in these animals. Analysis of the cellular make up of these organs revealed the enlargement of cortical and medullary areas, and pronounced pyroninophilia in the subcortical zone of the thymus and thymus-dependent areas of the spleen. The results suggest that Met-Enk exerts an immunorestorative activity in aged animals, and that changes in the opioid system may play an important role in the maintenance of immune functions during senescence.

Aging↗
PubMed1991

Immunostimulatory activity of prothymosin-alpha in senescence.

In this study we evaluated the immunorestorative activity of prothymosin-alpha (ProT-alpha) in senescence. Aged rats were repeatedly injected with ProT-alpha after antigen challenge. Both humoral and cell-mediated immune reactions were tested. The results show that ProT-alpha exerted a marked immunopotentiating effect in aged rats. Moreover, ProT-alpha induced enhancement of PFC response, and skin hypersensitivity reactions were more pronounced in senescent rats than in young adult controls. ProT-alpha treatment increased thymus and spleen weights in aged rats, and induced qualitative and quantitative improvements of the cellular make-up of the thymus and thymus-dependent areas of the spleen. The results imply that "restoring" thymus endocrine function by exogenous administration of ProT-alpha may improve immune system homeostasis in senescence.

Aging↗
PubMed1991

Magnetic fields, brain and immunity: effect on humoral and cell-mediated immune responses.

Magnetic fields (MF) can influence biological systems in a wide range of animal species and humans. We report here on the influence of static MF, locally applied to the brain area, on immune system performances in the rat. In the first series of experiments two AKMA micromagnets (M) with the influx density of 600 Gauss were bilaterally implanted (with "N" polarity facing the cranial bones) and fixed to the skull posterior to the fronto-parietal suture (parietal brain exposure). Rats implanted with iron beads (I) and sham-operated (SO) rats served as controls. Animals were exposed to MF or I during different periods of time before and after immunization with several soluble or cellular antigens. We report here on the in vivo immunoregulating effects of centrally applied MF on plaque-forming cell (PFC) response, local hypersensitivity skin reactions and experimental allergic encephalomyelitis. The selective influence of MF applied to different brain regions on PFC response was evaluated, as well. For this purpose, two M were bilaterally implanted in the area of (a) frontal, (b) parietal and (c) occipital brain regions. Rats were under the influence of MF for 20 days before and 4 days after immunization with sheep red blood cells. Groups of nonimmunized rats were exposed for 14, 24 and 34 days to parietally implanted M or I, and the number of peripheral blood CD4+ and CD8+ cells determined by mouse anti-rat W3/25 and MRC OX 8 monoclonal antibodies. The results show an overall in vivo immunopotentiation of humoral and cell-mediated immune responses in rats exposed to MF. Furthermore, these immunomodulating effects of centrally applied MF depend on at least two basic parameters, time of exposure and brain region exposed. The highest immune performance was obtained after exposure of the occipital brain region for a total period of 24 days. The results provide further evidence of the complex interrelationship between the environment, the central nervous system and the immune system.

Animals↗
PubMed1991

Enkephalinase-inhibitors modulate immune responses.

Exogenous opioid peptides, and enkephalins in particular, modulate a variety of immune performances in vivo and in vitro. In this study, the immunomodulatory role of endogenous opioids was investigated by means of central and peripheral administration of four peptidase inhibitors in the rat. Animals sensitized with sheep red blood cells (SRBC) were daily treated intraperitoneally (i.p.) with 0.2 mg/kg or 1 mg/kg of each inhibitor, or intracerebroventricularly (i.c.v.) with 0.02 mg/kg and 0.2 mg/kg of bestatin, des-tyrosine-methionine-enkephalin, (Des-Tyr1)Met-Enk; and actinonin, and 0.005 and 0.5 mg/kg of N-Carboxymethyl-phenilalanine-leucine,(N-C)Phe-Leu. Controls were injected i.p. and i.c.v. with saline. The results revealed that in animals treated i.p. with 0.2 mg/kg of bestatin and (N-C)Phe-Leu potentiated the plaque-forming cell (PFC) response and hemagglutinin production. In contrast, these immune responses were suppressed by 1 mg/kg. On the other hand, i.p. doses of 0.2 and 1 mg/kg of actinonin and (Des-Tyr1)Met-Enk potentiated humoral immune responses. When given i.c.v., all of the inhibitors used exerted clear dose-dependent immunomodulatory effects, i.e. increase in the PFC response and hemagglutinin production when given at lower doses (0.005-0.02 mg/kg), and decrease when injected with higher doses (0.2-0.5 mg/kg). These effects of enkephalin-related peptidase inhibitors, applied i.p. and i.c.v., suggest the involvement of endogenous enkephalins in immune mechanisms.

Adjuvants, Immunologic↗
PubMed1991

Changes of experimental allergic encephalomyelitis by methionine-enkephalin injected into lateral ventricles of the rat brain.

Our previous investigations have shown that the opioid peptide methionine-enkephalin (Met-Enk) modulates in vivo a variety of humoral and cell-mediated immune performances. In this study, rats bearing polyethylene cannulae permanently inserted into the lateral ventricles of the brain were used. Experimental allergic encephalomyelitis (EAE) was induced with guinea pig spinal cord in complete Freund's adjuvant injected into the left hind foot pad. The following groups of cannulated rats were tested: nontreated with Met-Enk or saline, intracerebroventricularly (i.c.v.) injected with saline, and i.c.v. treated with low (1 microgram/kg) dose of Met-Enk and high (1 mg/kg) dose of Met-Enk. Intact noncannulated rats sensitized for EAE served as an additional control. The results showed that i.c.v. treatment with 1 microgram/kg of Met-Enk significantly increased the incidence and severity of EAE. In contrast, injections of 1 mg/kg of Met-Enk produced a moderate decline of clinical EAE, but marked diminution of inflammatory lesions in the brain. Interestingly, histopathology of EAE was more pronounced in control rats treated i.c.v. with saline. On the other hand, control cannulated rats noninjected with saline exhibited a striking decrease of neurological and histopathological signs of the disease, thus indicating a suppressive effect of stress (surgical procedure) on EAE. In conclusion, the present study showing the central effect of Met-Enk on EAE when peptide was applied in the cerebral cavity, and earlier studies which revealed the peripheral effect on EAE when Met-Enk was administered intraperitoneally, suggests that Met-Enk exerts its immunomodulatory action both centrally and peripherally.

Animals↗
PubMed1991

In vivo effect of prothymosin-alpha 1 on humoral and cell-mediated immune responses in the young rat.

There is a large body of evidence for the role of thymosin peptides in immunogenesis and immunity. In this paper we report on the influence of prothymosin alpha 1 (ProT-alpha 1), a hormone-like peptide derived from the calf thymus, on humoral and cellular immune reactions in the rat. Young adults received intraperitoneal injections of ProT-alpha 1 in the periods before and after immunization with cellular and soluble antigens. ProT-alpha-treatment produced a dose-dependent increase of both humoral and cell-mediated immune responses. The thymus weight increased but not that of spleen. Treatment of nonimmunized rats with this polypeptide significantly elevated the number of CD4+ and decreased the number of CD8+ cells in the peripheral blood. The results suggest a potent immunostimulatory activity of ProT-alpha 1 and imply direct action of this polypeptide on T lymphocytes.

Adjuvants, Immunologic↗
PubMed1991

Euthyroid sick syndrome in children with acute viral hepatitis A.

According to the clinical findings, the activity of serum asparate aminotransferase (EC 2.6.1.1), alanine aminotransferase (EC 2.6.1.2) and the level of total bilirubin, 45 children with acute viral hepatitis A were divided into two groups: with mild and moderately severe degree of disease. By determining the products of the peripheral thyroxine metabolism-T3 and rT3, as well as the other thyroid parameters (T4, FT4, TSH and TBG) we have found significantly lower T3 level and significantly higher T4 and TBG levels in both groups of patients in comparison with control group. At the same time, the level of biologically less active rT3 was increased in patients with moderately severe form of disease, while no differences were found in the values of TSH between the ill and control patients. TRH induced TSH release was normal in all patients. The results of this study point to the development of euthyroid sick syndrome or low T3 syndrome in children with viral hepatitis A.

Acute Disease↗
PubMed1990

[Minor malformation score in congenital cleft of the lip and palate].

The authors analyzed minor malformation score in 63 children (36 boys and 27 girls) with congenital cleft of the lip and palate in order to evaluate purposefulness of its application as a screening method in detecting various major malformations. The results obtained revealed extremely increased minor malformation score in our patients and confirmed that an increased minor malformation score is associated with major malformation, i.e. clefts of the lip and palate. Therefore, it could be used as a screening method for detection of major malformations.

Cleft Lip↗
PubMed1987

Enkephalins and immunity. I: In vivo suppression and potentiation of humoral immune response.

BALB/c mice and Wistar rats immunized with sheep red blood cells and ovalbumin were treated intraperitoneally with different doses of methionine-enkephalin, leucine-enkephalin, and naloxone. Large doses of enkephalins (10-5 mg/kg b.w.) induced a significant decrease in hemolysin-forming cell response and production of hemagglutinating antibody. Immunosuppression induced by enkephalin was dose-dependent. In rats met-enkephalin was a more potent immunosuppressor than leu-enkephalin. Rats injected with 2.5 mg/kg b.w. of enkephalins into the lateral ventricle of the brain showed more pronounced immune suppression than did animals treated intraperitoneally with 5 mg/kg b.w. of enkephalins. These neuropeptides, and met-enkephalin in particular, exhibited a protective action against anaphylactic shock in rats sensitized to ovalbumin. In those animals, passive cutaneous anaphylaxis and elaboration of precipitating anti-ovalbumin antibody were considerably reduced. On the other hand, small doses of enkephalins stimulated humoral immune responses in the rat. Thus, it appears that enkephalins both suppress and potentiate immune responsiveness, depending on the dose used. As for naloxone, a large dose of this blocker of opioid receptors enhanced humoral immune reactions in the rat.

Adjuvants, Immunologic↗