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Biomedical subjects

D Marić

Publications and source records attributed to D Marić.

At least 37 records · Page 2Linked to original sources

[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↗

Enkephalins and autoimmunity: differential effect of methionine-enkephalin on experimental allergic encephalomyelitis in Wistar and Lewis rats.

To evaluate the immunomodulating activity of methionine-enkephalin (Met-Enk) and leucine-enkephalin (Leu-Enk) in the development of experimental allergic encephalomyelitis (EAE), two strains of rats, one highly susceptible to EAE (Lewis rats) and the other relatively resistant to the disease (Wistar rats) were used. The animals were given daily injections of either a high dose (5 mg/kg b.w.) or a low dose (0.2 mg/kg b.w.) of these opioid peptides, after receiving guinea pig spinal cord in combination with immunological adjuvants. A major conclusion from this study is that Met-Enk is a potent immunomodulator/regulator of the autoimmune disease, whereas Leu-Enk does not affect EAE. The high dose of 5 mg/kg b.w. of Met-Enk completely or significantly inhibited neurological signs and markedly diminished occurrence and intensity of histological lesions in the brain, and cervical, thoracic, and lumbar spinal cord. The loss of body weight, which accompanies EAE, was also prevented by a high dose of Met-Enk. In contrast, the low dose of 0.2 mg/kg b.w. of Met-Enk potentiated neurological and histopathological features of the disease. Nonimmunized rats injected with enkephalins for a period of 17 consecutive days showed neither neurological nor histological signs of EAE, nor signs of intoxication due to the application of enkephalins. Thus, these data establish a link between methionine-enkephalin and EAE, and suggest that this opioid pentapeptide might be important in the pathogenesis and prevention of the inflammatory autoimmune disease.

Animals↗

Enkephalins and anaphylactic shock: modulation and prevention of shock in the rat.

Wistar rats were sensitized for anaphylactic shock with ovalbumin and treated intraperitoneally with 10 injections of methionine-enkephalin and leucine-enkephalin (4 mg/kg of body weight). Both pentapeptides suppressed the development of systemic anaphylaxis after intravenous injection of a shocking dose of ovalbumin. Methionine-enkephalin completely protected the animals from fatal shock. The level of circulating IgE and precipitating anti-ovalbumin antibodies decreased in rats given 10 injections of enkephalins. Mast cell degranulation was significantly inhibited in these animals as observed at autopsy. A single intraperitoneal injection of 4 mg/kg body weight of methionine-enkephalin given 30 min before the challenge with shock-inducing dose of antigen was also effective, although to a lesser extent, in protecting animals from anaphylactic shock. One injection of leucine-enkephalin did not exhibit significant antishock activity. The results suggest that enkephalins, and methionine-enkephalin in particular, are potent modulators of the complex biochemical processes underlying the anaphylactic shock in the rat.

Anaphylaxis↗

Developmental pattern of the testicular androgen response to gonadotrophin stimulation in vitro and its modification by chronic hypoprolactinaemia.

Developing male rats were treated chronically with bromocriptine (BR, 3 mg/kg b.w. daily) to maintain severe hypoprolactinaemia throughout postnatal development. This treatment induced a precocious increase in Leydig cell numbers per testis and caused substantial, but age-dependent, modifications of the androgenic responsiveness of incubated hemi-testis preparations to stimulation with hCG. Most conspicuous were: (i) a decrease in sensitivity of the testis to hCG at the approach of adult age (due presumably to reduced responsiveness of the Leydig cells), and (ii) a precocious increase in the steroidogenic maximum of the testis at peripubertal age. This probably resulted from the precocious increase in Leydig cell numbers, which was able to mask the negative consequences of reduced androgenic capacity per Leydig cell. The precocious increase in number of Leydig cells induced by hypoprolactinaemia could have resulted from facilitation of the proliferative action of the high prepubertal LH levels on Leydig cell numbers. There were no clear-cut indications for an important effect of BR-induced changes in LH levels, or of a direct effect of BR on the testis.

Androgens↗

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↗

Enkephalins and immunity. II: In vivo modulation of cell-mediated immunity.

Body, thymus, and spleen weights, and cellular makeup of lymphoid tissues of rat were not affected to a great extent by intraperitoneal injections of met-enkephalin, leu-enkephalin, or naloxone. However, enkephalins induced a diminution of peripheral blood leukocytes and lymphocytes. In addition, met-enkephalin depleted the population of T4 helper/inducer lymphocytes. On the other hand, there was an increase of blood leukocytes and lymphocytes in naloxone-treated animals. Arthus and delayed skin hypersensitivity reactions to bovine serum albumin and old tuberculin were sharply reduced in enkephalin-treated rats. Rejection of allogenic thyroid graft implanted under the renal capsule was considerably delayed by repeated injections of enkephalins. Mesenteric mast cell degranulation in rats sensitized to ovalbumin and injected with a shocking dose of antigen was less pronounced after treatment with enkephalins. These results show that enkephalins, in dosage levels of 5 mg/kg b.w., exert a suppressive influence on cell-mediated immune reactions. Other experiments from our laboratory, reported in a companion paper in this volume, suggest that much lower doses may have opposite (immunoenhancing) effects.

Adjuvants, Immunologic↗

Rapid naloxone-induced alterations of androgen variables in the growing male rat.

Contrary to earlier views on the inability of naloxone to affect androgen variables by way of general circulation, systemically applied naloxone (2.5 mg/kg body weight, single i.p. or i.v. injection) has been shown to rapidly induce (within an hour) a significant fall (-35.7% on the average) of the concentration of serum androgen (testosterone and dihydrotestosterone; (T + DHT) in peripubertal rats (51-58 days old). Such a response to the opiate antagonist was absent, however, in low-androgen prepubertal animals (37-44 days old) and in those among peripubertal rats which still showed subcritical initial levels of androgen in circulation (less than 1.5 ng/ml; experiments with repeated blood sampling in catheterized animals). In peripubertal rats naloxone was also shown to induce a significant decrease (-36%) in basal in vitro androgen production by testes removed 15 or 30 min following the intraperitoneal administration of the opiate antagonist. Such an inhibitory effect on basal steroidogenesis has not been observed in control multiple-dose experiments in which incubated testes from naloxone-naive rats have been directly challenged with naloxone; on the contrary, enhancing direct effects were recorded, but only with the highest concentration of naloxone tested (10(-4) M). The possibility thus remains open that indirect inhibitory effects of injected naloxone may be operational in intact animals. Hypoprolactinemia, known to interfere in an age-dependent manner with the responsiveness of Leyding cells to luteinizing hormone (LH), may be of particular relevance.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Effects of bromocriptine-induced hypoprolactinaemia on the developmental pattern of androgen and LH levels in the male rat.

In immature male rats, receiving daily injections of bromocriptine (3 mg/kg bw), serum prolactin (Prl) remains low throughout development. In such hypoprolactinaemic males androgen variables are affected: a) the normally low pre-pubertal serum androgen (testosterone, dihydrotestosterone-T, DHT) is considerably increased, in correlation with a precocious development of the testicular Leydig cell population; b) the peri-pubertal rise of androgen is not prevented, but is is followed by significantly lower post-pubertal T, DHT levels, in correlation with moderately reduced Leydig cell counts and with strongly attenuated growth rates of sex accessory organs. Observed alterations of the post-natal androgen pattern cannot be related to LH changes since developmental LH values remained essentially unaltered. Results are in concordance with a marked age-dependent sensibility of androgen variables to a lack of Prl in the developing male.

Androgens↗