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The authors studied the relative bioequivalence and bioavailability of two oral polyamino-acid formulations (packet and flacon), based on 4 amino acids (L-glutamine, L-phosphoserine, L-phosphothreonine and L-arginine) in association with vitamin B12 (Bio-logos, Sigma Tau Pharma S.A). Open-trial testing was carried out after intensive treatment and on the attainment of sustained levels. 50 healthy volunteers (27 males, 23 females), ranging in age from 23 to 32 years, were included in the study. The pharmacokinetic behaviour of the various active ingredients was examined at a haematic level. Possible undesirable side-effects, resulting from treatment, were also examined during the study. The mean pharmacokinetic constants considered (Ke1, Cmax and t1/2) generated an almost overlapping AUC (area under the curves) for all homologous components contained in both pharmaceutical forms. This indicates almost complete bioequivalence. The mean index for the rate of relative bioavailability was, in fact, estimated to be 106.3 +/- 12.4%. Repeated treatment did not appear to disturb the absorption mechanisms of the active ingredients contained in either of the two formulations examined, maintaining the relative bioavailability relationship within a negligible range, with a statistically non-significant difference (Student's t test for coupled data). A few episodes, characterized by slight increases in excitability, were reported for both preparations in two patients (4%).

We have studied the effect of intravenous injection of eel calcitonin (ECT) on creatine kinase E.C.2.7.3.2. BB isozyme (CKBB) in the kidney of male Wistar rats. CKBB immunoreactivity was detected by the peroxidase-antiperoxidase method. Eel calcitonin increased CKBB immunoreactivity in the renal medulla in a dose-dependent fashion. Its effect peaked at 2 h and lasted up to 24 h. The distribution of activated CKBB in the kidney occurs in the same areas where highly specific CT-binding sites have been previously demonstrated, and is in agreement with the current concepts on renal actions of this hormone.

Post-translational modifications of chromatin-bound proteins play an important role in the regulation of eukaryotic gene expression. Processes such as acetylation, methylation, phosphorylation and ADP-ribosylation may alter the interaction of these proteins with DNA and consequently affect chromatin conformation and the binding of enzymes and other molecules involved in the regulation of gene expression. In the present study the process of ADP-ribosylation of chromosomal proteins (histone and non-histone proteins) in some rat brain regions during postnatal development was investigated; also the effect of epidermal growth factor (EGF) on this process in fetal brain slices was studied. It has been found that the process of ADP-ribosylation of total histones extracted from rat cerebral cortex and cerebellum at 1, 10 and 30 days of age, increases from 1 to 10 days of age (i.e. the period of maximal cell proliferation) and decreases thereafter, while the process of ADP-ribosylation of non-histone proteins (NHPs) sharply decreases during the same developmental period. The addition of EGF to fetal brain slices causes a significant increase of ADP-ribosylation of total histones (particularly of the histone H1 fraction) and also of NHPs and microsomal proteins. This result is in agreement with the effect of EGF as a mitogen factor, previously shown in astroglial cell cultures.

Results of experiments in cell cultures suggested that epidermal growth factor might influence an early stage of astroglial or neuronal cell differentiation. In order to evaluate this hypothesis the effects of subcutaneous and intracerebral treatment with epidermal growth factor on glutamine synthetase, an astroglial marker enzyme, and glutamate decarboxylase activity, a marker enzyme of GABAergic neurons, were investigated during postnatal development of mouse brain. Epidermal growth factor, at the dose used, induced the well-known effects of the in vivo treatment, such as a decrease in body weight and a precocious incisor eruption and eyelid opening. A decrease in forebrain and cerebellum wet weight was also observed. However, repeated epidermal growth factor treatment, during early postnatal life, failed to influence glutamine synthetase activity in forebrain or cerebellum, while a significant decrease was observed in the brain stem. No effect of epidermal growth factor on forebrain glutamate decarboxylase activity was observed. Although epidermal growth factor receptors have been detected in the newborn rodent brain, the role of this growth factor in brain development remains to be elucidated.

We examined the effects of age on RNA and lipid formation by whole retina and optic nerve in vitro. Male Wistar rats, aged 4, 12, and 24 mo, were used. From the results obtained the following conclusions may be drawn: 1. In assaying the lipid biosynthesis during aging, a striking difference between the retina and optic nerve clearly emerged; 2. In isolated retina, [3H]uridine incorporation into RNA was relatively constant at the three ages, whereas both [14C]palmitate and [3H]choline incorporation into lipids showed a substantial increase in rats at 24 mo of age compared with those at 4 mo; 3. In contrast, in the optic nerve of the oldest rats, compared with the youngest, a significant decrease of [14C]acetate and [14C]palmitate incorporation into acylglycerols, cerebrosides, and phospholipids was found. Each fatty acid precursor label was incorporated to a proportion that reflected the typical acyl group composition of individual lipids; 4. Following labeling of the optic nerve with [3H]choline, the specific radioactivity of choline-containing phospholipids was drastically decreased with increasing rat age; and 5. The incorporation of [2-3H]glycerol into optic nerve diacylglycerols, PtdEtn, and PtdIns declined with age, whereas no significant change took place in the incorporation into PtdCho. The results strongly support the concept that RNA metabolism of rat retina (most likely photoreceptor cell layer) is not altered during aging; on the contrary, phospholipid synthesis is stimulated in comparison with that of the optic nerve, for which a serious impairment was concomitantly observed. The physiological significance of these responses, and the mechanism by which retinal tissue is spared from the general age derangement of the nervous system, remain to be defined.

An increase in astrocyte mitogenic factors and in some specific astroglial enzymatic activities after neuronal injury has been observed. Our study is concerned with the effect of the intracerebral administration of ibotenic acid (IBO) into the rat hippocampus. IBO injection causes a selective degeneration of neurons while sparing afferent fibers. We observed a transient increase in glutamine synthetase activity, a well-known astroglial marker, reaching a peak at 9-15 days after injury in lesioned hippocampus. We investigated the presence of astrocyte mitogenic factors at various times after toxin injection. Crude extracts, prepared from lesioned hippocampi 4, 9, and 14 days after IBO injection, were tested for the ability to stimulate [methyl-3H]thymidine incorporation into rat astroglial cell cultures. Crude extracts prepared 9 and 14 days after IBO injection showed a higher mitogenic activity compared to extracts prepared 4 days after lesion. Mitogenic activity of injured brain extracts was suppressed by heat inactivation (100 degrees C for 10 min).