The hypothalamus and protein metabolism in rats.

Using the technique of mechanical isolation of the medial hypothalamus from the rest of the CNS, it has been concluded--based on total serum protein content, protein fractions as well as total serum amino acids--that under resting conditions the hypothalamic influence upon protein metabolism is achieved through the control exerted upon endocrine system rather than by a direct neural mechanism. The authors' results show that aminoacidemia is not a determining factor in feeding behaviour.

Feeding behaviour in rats with isolated medial hypothalamus as a function of ambient temperature.

The experiments of mechanical isolation of medial hypothalamus from the lateral hypothalamus and the preoptic anterior hypothalamic (POAH) region in rats showed that: 1. The interruption of neural connections between POAH area and medial hypothalamus do not prevent the decrease of food intake which normally occur in a hot environment. 2. At 33 degrees C, hyperphagic rats gained more weight than sham-operated ones. 3. At 4 degrees C, rats made hyperphagic by hypothalamic isolation do not ajust their food intake for a long period and do not gain weight. 4. The excitatory pathways of the feeding center from the POAH area do not penetrate directly into the lateral hypothalamus, but rather into the medial retrochiasmatic area. 5. The temperature influences the diurnal pattern of feeding only in rats with intact or unilateral neural connections of the hypothalamic structures 6. It seems that the thermostatic mechanism, which is a potent regulator of feeding, is closely associated with the central control of thyrotropin release, and that the hypothalamic structures may be considered only as a necessary link in the nervous mechanism involved in feeding control.

The effect of partial or total medial hypothalamic isolations on lipid metabolism in rats.

Medial hypothalamic isolation in the rat occurring under free food acces or after 24 hours starvation determines a significant increase in serum lipemia, serum esterified fatty acids and carcass fat. A significant rise in carcass fat was evident in rats made hyperphagic by medial hypothalamus isolation and maintained on limited food intake. It has been concluded that the VMH nuclei are involved in the control of the lipid metabolism primarily through the inhibitory effect exerted on the lateral hypothalamic parasympathetic area.

Feeding behavior in the rat with isolated medial hypothalamus.

After complete, unilateral, frontolateral, dorsal isolation of the medial hypothalamus, VMH included, or fornix section above the hypothalamus, total food consumption and diurnal pattern of food intake were followed 85 days postoperatively. It is suggested that the saftety signals are generated not only in VMH nucleus, but in a VMH-retrochiasmatic region located anteriorly to the VMH.

Carbohydrate metabolism in rats after partial or total isolation of the medial hypothalamus.

After medial hypothalamic deafferentation at complete (CD), frontal (FD), or frontolateral (FL) levels, at the same time with adrenocortical hormone determination, sensitivity to insulin and insulinemia were determined at a postoperative time, when adenohypophyseal hormonogenetic process concerned to ACTH and growth hormone, is reverted to the normal. The glucose assimilation coefficient (K) was followed weekly for a month postoperatively. Insulin sensitivity decreased after CD and increased after FD. FL and CD rats had significantly elevated plasma insulin level, despite normoglycemia. The changes recorded in plasma insulin level and sensitivity to insulin are attributed primarily to the CNS defect. After hypothalamic isolation, K is unchanged. This might point to the creation of new set point for hypo- and hyperglycemiating system, respectively. We concluded that the presence of nervous connections of the medial hypothalamus with surrounding nervous structures is necessary for a normal carbohydrate metabolism control.

Lipid metabolism in rats with isolated medial hypothalamus.

Based on determinations of the serum total cholesterolemia, triglyceridemia, free fatty acids and obesity Lee index, performed in rats with isolated medial hypothalamus--VMH included--which had either free food access, or after 24 hours of starvation, or maintained on limited food intake, it has been concluded that the VMH nucleus is involved in the control of lipid metabolism especially through its inhibitory action on the lateral hypothalamic parasympathetic area.

[Ginkgo biloba extract (EGb 761) as an antioxidant factor of exogenous origin]. / Cercetari privind extractul de Ginkgo biloba (EGb 761) ca factor antioxidant de natura exogena.

Extracted from Ginkgo biloba leaves, the EGb 761 has a great number of therapeutical properties and anti-stress effects, for example the antioxidant one. We estimated in our experiment the influence of a chronic treatment with EGb 761 on the concentration of the main product of lipidic degradation--malondialdehyde (MDA), in cerebral cortex, in diencephalon, thymus and gastric mucosa. The experiment was performed on Wistar rats, male, young. The MDA estimation was performed by the spectrocalorimetry. We have determined that the stress raised the MDA concentration in all examined structures with approximately 100% and 80% of animals manifested stress ulcer. The treatment with EGb 761 before a stress inhibits the post-stress growth of MDA concentration and the process of stress ulcer formation.

The ways through which the hypothalamic paraventricular nucleus (PVH) and the medial hypothalamus affect the organism's defence function.

In the rats, mechanical lesion or isolation of the PVH either alone or together with the medial hypothalamic sympathetic area, which includes hypophyseotropic area, too, induces a long lasting decrease of the total number of leukocytes and of the most components of the leukocytary formula, which are attributed mainly to the decreased sympathetic tonus, induced by medial hypothalamus disconnection.

The role of the hypothalamic paraventricular nucleus upon the activity of thyroid and adrenal glands and their relation with body defense function.

Lesion of the PVH or its isolation--either alone or together with the medial hypothalamus, at fronto-lateral or complete level, induces a significant decrease in plasma thyroxine and a negligible modification of triiodothyronine. Variations recorded with various groups, having the medial hypothalamus deconnected, suggest that the main thyroliberin secreting (TRH) region is located at the level of PVH. Immunization of animals restores the thyroid function in the animals with damaged PVH, under the action of thyrotropin (TSH) of lymphocyte origin. Although the main CRH source occurs at the level of PVH, the results obtained after lesions or isolations of the hypophysotropic region demonstrate the extended distribution of CRH within various nervous areas, and its possible involvement in maintaining the adrenal gland function.

Memory deficits and increased emotionality induced by beta-amyloid (25-35) are correlated with the reduced acetylcholine release and altered phorbol dibutyrate binding in the hippocampus.

In the present study we found that chronic infusion of beta-amyloid fragment (25-35) at nanomolar concentration into rat cerebral ventricle impairs learning and memory. At a concentration of 3 nmol/day but not 0.3 nmol/day, beta-amyloid significantly reduced the spontaneous alternation behavior and the memory performance in the water maze and multiple passive avoidance tests. A significant increase in anxiety was also found in the animals infused with 3 nmol/day beta-amyloid fragment. Memory deficits and the increased emotionality were correlated with a decreased nicotine-evoked acetylcholine release from the frontal cortex/hippocampus, as assessed by microdialysis, in freely moving rats. The amyloid fragment infused either at pico- or nanomolar concentrations reduced the affinity of [3H] phorbol dibutyrate binding, an index of activated protein kinase C (PKC), and increased the total number of binding sites in the hippocampal particulate fraction. Our results suggest that the amnesic and anxiogenic effects of chronic infusion of beta-amyloid (25-35) are related to the decreased acetylcholine release and reduced PKC activation.

The interaction between the cholinergic and dopaminergic system in learning and memory process in rats.

In normal rats, muscarinic acetylcholine receptors (mAChRs) have a facilitating role on both short-term and long-term memory tested by Y-maze task and multi-trial passive avoidance test, respectively, since scopolamine, a specific mAChRs antagonist, impairs both types of memory. A low dose of nicotine (0.3 mg/kg b.w., i.p.), a specific nicotinic acetylcholine receptors (nAChRs) agonist, administered once caused a significant facilitating effect on short-term memory. A higher dose of nicotine (3 mg/kg b.w., i.p.) administered 5 consecutively days had about the same facilitating effect on short- and long-term memory without affecting information acquisition. In rats, having mAChRs and nAChRs blocked by means of scopolamine and chlorisondamine respectively, a low dose of nicotine administered once caused a significant improvement of long-term memory deficits without affecting significantly short-term memory. A higher dose of nicotine administered 5 consecutive days in rats with a double blockade of cholinergic receptors had the same ameliorating effect on long-term memory deficits as low dose. Our data suggest that the antiamnesic effect of nicotine can result from an action at nicotinic receptors subtypes not blocked by chlorisondamine or at nonnicotinic receptors.

Polyurethanes based on dihydroxamic acids. Synthesis, chemical characterization, and biological activity.

A series of segmented polyurethanes based on polyethylene oxide/polycaprolactone diol, isophorone diisocyanate, and dihydroxamic acids were synthesized and characterized. Biocompatibility and antitumoral activity were in vivo tested on Wistar male rats and Wistar rats affected with Walker 256 carcinosarcoma, respectively. The effect of dihydroxamic acid structure on the biological properties was determined. A better antitumoral response of the polyurethanes containing aliphatic dihydroxamic segment compared with those which resulted using terephthaloyl dihydroxamic acid was evidenced. With increasing polymer chain polyethylene oxide content the antitumoral activity was also enhanced. Some attempts on the in vitro biodegradation of above polyurethanes were also performed.