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Biomedical subjects

L Milenković

Publications and source records attributed to L Milenković.

At least 19 recordsLinked to original sources

Altered neural cell fates and medulloblastoma in mouse patched mutants.

The PATCHED (PTC) gene encodes a Sonic hedgehog (Shh) receptor and a tumor suppressor protein that is defective in basal cell nevus syndrome (BCNS). Functions of PTC were investigated by inactivating the mouse gene. Mice homozygous for the ptc mutation died during embryogenesis and were found to have open and overgrown neural tubes. Two Shh target genes, ptc itself and Gli, were derepressed in the ectoderm and mesoderm but not in the endoderm. Shh targets that are, under normal conditions, transcribed ventrally were aberrantly expressed in dorsal and lateral neural tube cells. Thus Ptc appears to be essential for repression of genes that are locally activated by Shh. Mice heterozygous for the ptc mutation were larger than normal, and a subset of them developed hindlimb defects or cerebellar medulloblastomas, abnormalities also seen in BCNS patients.

Abnormalities, Multiple↗

Inhibition of gonadotropin hormone-releasing hormone release by prolactin from GT1 neuronal cell lines through prolactin receptors.

High levels of prolactin (PRL) are associated with inhibition of luteinizing hormone secretion in several mammalian species. We asked whether this phenomenon could be explained by a direct inhibitory action of PRL on hypothalamic gonadotropin hormone-releasing hormone (GnRH) neurons. The ability of PRL to suppress GnRH release and expression was tested in the highly differentiated GT1 GnRH cell lines. In static culture, nanomolar concentrations of either rat or mouse PRL inhibited the release of GnRH in a dose-dependent fashion. PRL treatment for 24 hr also decreased GnRH mRNA levels determined by Northern analysis. The cells were shown to express the PRL receptor gene, and the mRNAs for both the short and long forms were present by Northern and PCR analysis, although the short form was more abundant. In Western blots with monoclonal antibody against the rat liver PRL receptor, the short 42-kDa form of the receptor was observed. These results demonstrate that PRL inhibits GnRH release and possibly gene expression in GnRH neurons. This action appears to be mediated through prolactin receptors expressed by the cells.

Animals↗

Application of therapeutic plasma exchange in hematology.

Therapeutic plasma exchange (TPE) was used in 146 patients with hematologic disorders: hyperviscosity syndrome, 74; cryoglobulinemia, 53; porphyria, 9; immune complex disease, 3; cold agglutinin disease, 1; hemolytic uremic syndrome, 1; autoimmune hemolytic anemia, 1; autoimmune thrombocytopenia, 1; autoimmune neutropenia, 1; Clq deficiency, 1; and secondary immunodeficiency, 1. It was shown that TPE applied in patients with hyperviscosity syndrome resulted in rapid reduction of paraprotein concentrations, and normalization or significant decrease of serum viscosity associated with marked clinical improvement (regression of neurologic, renal, hematologic, visual and other disturbances). Application of TPE in patients with cryoglobulinemia resulted in plasma cryoglobulin reduction and clear clinical effects (blood flow improvement, skin ulcer healing, reversal of impaired renal function and disappearance of purpura and other abnormalities). Very good results were obtained in patients with porphyria (decreased sensitivity to sunlight) and also in patients with Clq deficiency. Satisfactory clinical improvement and better laboratory findings were also seen in patients with immune complex disease, autoimmune hemolytic anemia, autoimmune thrombocytopenia and hemolytic uremic syndrome.

Evaluation Studies as Topic↗

The role of neuropeptide Y (NPY) in control of gonadotropin and prolactin release in the rat.

Neuropeptide Y is a peptide found in a variety of hypothalamic loci which is frequently colocalized with catecholamines. It is also secreted into hypophyseal portal vessels. We have previously evaluated the effects of this peptide on FSH, LH and prolactin release. In ovariectomized females neuropeptide Y inhibits LH release. It has similarly been reported to inhibit LH release in intact males; however, estrogen priming of ovariectomized animals converts this inhibitory action into a stimulatory effect. In ovariectomized animals the peptide has a direct stimulatory effect on perifused pituitary cells, enhancing the release of both FSH and LH, an effect which is contrary to that obtained with LH release after intraventricular injection of the peptide. In the present experiments the physiological significance of these effects has been evaluated by the intraventricular injection (3V) of highly specific antiserum directed against the peptide. In ovariectomized and in ovariectomized, estrogen-primed rats, the third ventricular injection of antiserum had no effect on gonadotropin release. In male rats intraventricular injection of the antiserum elevated LH, which indicates that the inhibitory action of the peptide seen in intact males is of physiological significance. However, it has been reported by others that the proestrous type discharge of LH-RH is blocked by intraventricular injection of neuropeptide Y antiserum. Neuropeptide Y might therefore play an essential role in the preovulatory release of LH. On the other hand, others have shown that intraventricular injection of neuropeptide Y in male rats can either stimulate, at low doses, or inhibit, at high doses, the release of prolactin. We have confirmed the inhibitory action, which appears to be of physiological significance since antisera directed against the peptide injected intraventricularly resulted in an elevation of prolactin release. The results of these studies indicate that neuropeptide Y plays a very important and often physiologically significant role in the control of LH and prolactin release by hypothalamic action.

Animals↗

Ca2+ uptake by rat brain region synaptosomes following in vivo administration of ovarian steroids.

Effects of progesterone (P) and estradiol-17 beta benzoate (EB), applied s.c. into sexually mature, long-term ovariectomized (OVX) rats, on subsequent depolarization-induced uptake of Ca2+ were studied in synaptosomes isolated from the brain stem, mesencephalic reticular formation (MRF), nucleus caudatus putamen (NCP) and the hippocampus. In intact animals, synaptosomal Ca2+ uptake differed from region to region: it was lowest in the brain stem and highest in the hippocampus. In comparison to intact animals, ovariectomy resulted in a marked increase of the uptake regardless the structure investigated, suggesting an inhibitory action of ovaries on the uptake of Ca2+ in a considerable portion of rat brain. Single injection of 2 mg P, given to OVX rats 24 h prior to decapitation, evoked a marked decrease in Ca2+ uptake by synaptosomes of the brain stem and MRF and particularly by those of NCP and the hippocampus. Single injection of 5 micrograms EB into OVX animals 72 h prior to the experiment was as effective as P in inhibiting Ca2+ uptake by synaptosomes of the brain stem and MRF, but less effective than P in case of NCP and the hippocampus. This suggests involvement of P and EB in the modulation of synaptic transmission by affecting neuronal Ca2+ uptake.

Animals↗

Effects of oestradiol and progesterone on stress-induced secretion of prolactin in ovariectomized and/or adrenalectomized female rats.

Prolactin (Prl) secretion in response to an acute stress was studied in ovariectomized (OVX) and/or adrenalectomized (ADX) adult female rats, nontreated or injected sc with a single dose of 5 micrograms oestradiol-17 beta benzoate (OB) or 2 mg progesterone (P). The stress applied consisted of cutting the tip of tail of conscious animals. Radioimmunoassay was used to measure Prl in the serum prepared from blood collected by decapitation 10 min following the stress, i.e., at the point of maximum recorded Prl response. It was found that the capacity of the animals to secrete large quantities of Prl under stress was, when compared to that in intact controls, markedly reduced in OVX or ADX rats and substantially absent in OVX + ADX rats. A 10-fold increase of basal serum Prl, similar in magnitude to the increase in intact controls, was induced by the stress in OVX animals pretreated with OB. On the contrary, pretreatment of OVX animals with P resulted in a complete block of the Prl response to the stress. The stimulative effect of OB was greatly attenuated in stressed OVX + ADX rats. The results suggest that OB potentiates whereas P attenuates the stress-induced secretion of Prl in the female rat, and that the potentiating effect of OB is dependent on functionally intact adrenals.

Adrenalectomy↗

Effects of aging on prolactin release after stress in female and male rats.

Young adult and elderly male and female intact rats, as well as chronically ovariectomized (OVX) young and elderly female rats, were subjected to an acute stress by cutting the tip of the tail and prolactin (Prl) concentrations were measured in their blood collected by decapitation at various times thereafter. Maximum concentrations of the hormone were markedly lower in all the three groups of elderly rats than those found in the corresponding young animals, and appeared to occur with a delay in the females, but not in the males. In addition, the Prl-response to stress was attenuated in OVX animals regardless of their age. The result of these experiments, performed at two points on the age scale, suggests that in sexually mature rats of both sexes the stress-induced secretion of Prl is inversely related to the age of the animal and that the reverse relationship is retained in OVX females.

Aging↗

[Albumin and its therapeutic use - part I].

Albumin is most abundant and most studied protein of the circulation. Its biosynthesis is closely dependent on the nutrition, amino acid supply, hormonal millieu, environment, osmotic equilibrium, diseases and some other factors. Albumin is synthetized in the liver on a polyscmes and delivered into the blood streem. Degradation of albumin is practically still unknown and is one of many biological puzzles. Albumin prepared for therapeutic use almost contains dimers, oligomers and polymers which are very important, because they are one of the parameters for evaluation of albumin products quality.

Humans↗

[Albumin and its therapeutic use - Part II].

Albumin is the most effective oncotic agent and has wide clinical application. In the resuscitation of injured patients with hypovolemic shock (during war and peace) the use of supplemental albumin is purported to be more effective in restoring plasma volume, increasing cardiac output, preventing pulmonary oedema and maintaining organ perfusion than resuscitation without supplemental albumin. Most important in a study of albumin are criterias for appropriate use because it was sometimes unjustified. Therapeutic use of albumin should not be dictated by arbitrary or pragmatic restriction but rather by rational prescribing from physicians well educated in its use.

Adult↗

[The quality of preserved blood].

The examinations of 30 blood samples each preserved with three Yugoslav different ACD-solutions were performed. The blood samples were stored at 2-6 degrees C and examinations were performed at the day of blood donation and after on the 7th, 14th and 21st day during the storage. Differences in hematocrit (well known dilution effect of the ACD-solutions used) and intensive morphological and chemical changes were found in all blood samples regardless the type of ACD-solution used. It was shown that the permanently increasing number morphologically altered erythrocytes (echinocytes and spherocytes) and the excessive release of hemoglobin and potassium from erythrocytes were occurred during the storage of blood samles. Too, there were noticed significant decrease of pH values enormous accumulation of ammoniac and other metabolic producta.

Ammonia↗

[Transfusion-infusion methods in the treatment of acute poisoning].

For modern acute poisoning management there are several therapeutic transfusion-induced methods (forced diuresis, haemodialysis, peritoneal dialysis, haemoperfusion, plasmapheresis, exsanguino-transfusion, blood and blood component transfusion, intravenous solution infusion etc), each of them having their advantages, disadvantages and limitations. No one of these methods is so efficacious enough that its application could be justified in all poisonings. However, some of them are considered to be method of choice in the treatment of certain acute poisonings.

Blood Transfusion↗

Effects of unilateral castration on the hypothalamic structures involved in the regulation of gonadal function in rat.

This study was undertaken to evaluate the effects of unilateral gonadectomy on the hypothalamic structures involved in the regulation of gonadal function in adult rats of both sexes. Unilateral gonadectomy was performed; 15 days later stereological parameters of cell activity of both the halves of hypothalamic preoptico-suprachiasmatic area (PO-SC) and arcuate nucleus (NA) were analyzed. Under the same experimental conditions the activities of the FSH and LH immunoreactive cells were analyzed separately in both the halves of the adenohypophysis. The results showed that in the rats of both sexes subjected to unilateral gonadectomy the mean diameter of cell nuclei of the contralateral half of PO-SC was significantly greater than that of the ipsilateral half. However, in the control intact or bilaterally gonadectomized rats, there were no significant differences in the values of the same parameter between two halves of PO-SC. On the other hand, neither in the unilaterally gonadectomized nor in the controls, the values of the mean diameter of NA cell nuclei differed significantly between the two halves of this structure. The FSH and LH pituitary cells behaved like NA cells. Therefore, since in the experimental animals compensatory function was developed, and since nervous signaling was different from the sides of the removed and intact gland, the present results suggest involvement of a pure nervous mechanism, besides hormonal control, in the regulation of the compensatory gonadal function. This mechanism seems to be functional in the rats of both sexes. These results also indicate that PO-SC is the anatomical structure involved in this regulation.

Animals↗

[Fibrin glue in tympanoplasty].

In order to achieve more favourable anatomic and functionally more permanent position of the transmission materials, fibrin glue was applied in 68 patients undergoing different microsurgical interventions for the cure of inflammatory processes in the middle ear or improvement of conductive deafness of inflammatory or traumatic origin. Fibrin glue has shown to be equally suitable both in fixation of the biological materials - homografts and autografts and in fixation of alloplastic prostheses. The efficacy of preservation of the best position was demonstrated in all forms of direct collumelas, ossicular graft interposition, closure of the labyrinthine fistulas and reconstruction of the external attic wall.

Fibrin Tissue Adhesive↗