MTHFR C677T polymorphism modifies the effect of HRT on metabolic parameters in postmenopausal women.

OBJECTIVE: To assess the interaction of the MTHFR C677T polymorphism with changes in lipid and glucose metabolism effected by oral hormone replacement therapy (HRT) in postmenopausal women. METHODS: In this open-label, prospective, interventional study, parameters of lipid and glucose metabolism, as well as homocysteine, were assessed in 97 postmenopausal women at baseline and 1 year after the initiation of HRT. Participants were stratified into three subgroups, according to the MTHFR C677T polymorphism (wild-type: CC genotype; heterozygous: CT genotype; homozygous for the mutant variable: TT genotype). RESULTS: The TT genotype was associated with an elevation of total and low density lipoprotein (LDL) cholesterol, while CT and CC genotypes were associated with a reduction of total cholesterol and LDL cholesterol after 1 year of HRT (p = 0.032 for total cholesterol and p = 0.002 for LDL cholesterol). Women with the TT genotype had higher glucose levels in contrast to women with the CC genotype who had lower glucose levels after 1 year of HRT (p = 0.011). Additionally, CC carriers under HRT had a significant elevation of apolipoprotein A1 levels (p = 0.018), contrarily to CT and TT genotypes. CONCLUSION: While HRT was associated with favorable changes in lipid and metabolic parameters in carriers of the CC genotype, this effect was not evident in carriers of the T allele. The MTHFR C677T polymorphism may modify the effect of HRT on lipid and metabolic parameters in postmenopausal women.

Ultrastructural alterations of the rabbit sciatic nerve, spinal cord and cerebellum, following methionine sulphoximine administration.

Methionine sulphoximine (MSO) is a centrally acting neurotoxin which inhibits the glutamate metabolism enzymes and has convulsive properties. Small doses of MSO were administered to rabbits, either intravenously (i.v.) or intracerebroventricularly (ICV), and electron microscopic examination of the cerebellum, the spinal cord and the sciatic nerve was performed on the first day of rabbit hind leg rigid paralysis (myopathy with histological findings resembling myositis), which set in by the 2nd to 4th day after MSO administration. In the cerebellum focal minor alterations were found in the astrocytes (swelling and lucidity, diminution of glycogen granules) and sparsely in the presynaptic terminals (lucidity and clumping), whereas most of the neuron presented a normal appearance. In the spinal cord and in the sciatic nerve a dissociation of the axon from the myelin sheath was evident in a small number of myelinated nerve fibres, along with the appearance of vacuolated spaces. Mitochondrial disorganisation in the axons, as well as glial cell alterations, were also seen. The ultrastructural alterations were non specific, and since they were induced 2 to 4 days after the administration of either minimum doses (i.v.) or of extremely low doses (ICV) of MSO, they may be attributed to the inordinate increase of metabolism during the period of convulsions.

Long-term effects of the administration of the convulsive substance DL-methionine-DL-sulfoximine to the rabbit.

Methionine sulfoximine (MSO) is a centrally acting neurotoxin which inhibits the glutamate metabolism enzymes and has convulsive properties. Administration of a small dose of MSO to rabbits, either intravenously or intracerebroventricularly, except for the already known convulsive effects, may also be responsible for hind leg myopathy (rigid paralysis with histological findings resembling myositis) which sets in by the 4th day after MSO administration.

Biomagnetic methodologies for the noninvasive investigations of the human brain (MAGNOBRAIN).

Magnetoencephalography (MEG) non-invasively infers the distribution of electric currents in the brain by measuring the magnetic fields they induce. Its superb spatial and temporal resolution provides a solid basis for the 'functional imaging' of the brain provided it is integrated with other brain imaging techniques. MAGNOBRAIN is an applied research project that developed tools to integrate MEG with MRI and EEG. These include: (1) software for MEG oriented MRI feature extraction; (2) the Brain Data Base (BDB) which is a reference library of information on the brain used for more realistic and biologically meaningful functional localisations through MEG and EEG; and (3) a database of normative data (age and sex matched) for the interpretation of MEG. It is expected that these tools will evolve into a medical informatics environment that will aid the planning of neurosurgical operations as well as contribute to the exploration of mental function including the study of perception and cognition.

Involvement of the caudate nucleus in the modulation of the brain somatosensory evoked potentials.

The participation of the caudate nucleus in the modulation of the cortical somatosensory evoked potentials was investigated in male rabbits. The power spectra of the somatosensory evoked potential recorded from the scalp in the intact animal was compared with that recorded after kainic acid lesion of specific regions of the caudate nucleus (i.e., anterior and or posterior portions of the head of the nucleus) and the "destructive" interference patterns which appeared were investigated. It was found that the caudate's head modulates the waveform at the end of the early phase of the cortical somatosensory evoked potentials, i.e., the period from 20.8 ms to 29.4 ms. These results suggest that the caudate nucleus is part of the sensory pathways belonging to the nonspecific projection system and participates in the integrating processes of the somatosensory information.

Effects of intracerebroventricular administration of atrial natriuretic peptide on subcortical EEG activity in conscious rabbits.

Atrial natriuretic peptide (ANP) influences the activity of rat hypothalamic neurons, modifies the membrane excitability of the rat forebrain neurons, and induces changes in membrane potentials in cultured rat glioma cells. In order to explore whether these effects are reflected in the electrical activity of larger subcortical brain areas, we investigated the electroenceophalographic activity (EEG) recorded from 20 male albino (New Zealand White) rabbits. Recordings of EEG were made on restrained, conscious animals 1 week after the implantation of an indwelling intracerebroventricular (i.c.v.) cannula (lateral right ventricle) and two stainless steel electrodes, implanted in the paraventricular (PVN) and supraoptic (SON) nuclei. Animals were classified into two main groups: those with water available ad libitum (group A) and those which were dehydrated for 24 h before EEG recordings (group B). Each group was divided into two subgroups (1 and 2) of five animals each. EEG was recorded at 0 min (control) and 30, 60, and 90 min following the i.c.v. injection of either 25 microliters artificial cerebrospinal fluid (aCSF; subgroup 1) or 1 microgram alpha-human ANP in 25 microliters a CSF (subgroup 2). Each EEG record duration was 6 s. For each EEG record the power spectrum of the digitized waveform was estimated in the frequencies 0.5-48 Hz using the fast Fourier transform, and the energy of each waveform was subsequently calculated. The results were analyzed by repeated-measures ANOVA and by the t-test. The analysis revealed that (1) water deprivation does not affect mean EEG energy and value (2) ANP attenuates (P < 0.05; in comparison with zero time) the mean energy value of EEG recorded from SON at 30 min and 60 min in the frequencies 8-48 Hz, whilst it tends to decrease (P < 0.1) the mean energy of EEG recorded from PVN at 30 min in the frequencies 8-15 Hz. Mean EEG energy changes caused by ANP would reflect its various (mainly inhibitory) effects on the electrical activity recorded from PVN and SON neurons in in vitro and in vivo studies.

A neural net model for the release of prolactin during pseudopregnancy in the rat.

A theoretical probabilistic neural net model is proposed here based on the interaction between two subsystems, the connections of which are made up by means of chemical markers. The activity of such a system at t = n tau is exclusively dependent on the firing record of the system at t = (n-1) tau, on the level of spontaneous activity and on an external inhibitory influence which we have found that may play an important role in the prolactin release level during pseudopregnancy in rats. We explore some of the implications of this model on the possible role of the hippocampus in the phenomenon.

Work capacity, contractile protein and quantitative electromyogram (EMG) changes following exercise or nandrolone decanoate treatment in experimentally induced muscle disuse atrophy in rats.

Anabolic steroid administration and planned exercise have been the two main methods applied to improve the function and morphology of atrophied muscle tissue. The effects of these two factors-specifically nandrolone decanoate administration and exercise by swimming on muscle weight, EMG activity, work capacity and on contractile protein content of rat gastrocnemius muscle, following experimentally induced atrophy by immobilization, were investigated. The results appear to support the conclusion that although both types of treatment obtain significant positive results exercise acts more effectively than the anabolic steroid in this respect.

Effects of growth hormone and triiodothyronine administration of the localization of 14C-D-glucose on regenerating sciatic nerve in rabbits.

In the present study the effect of the administration of GH and T3 on glucose distribution in the regenerating nerve was studied. The right sciatic nerve of 40 male rabbits was crushed at a specific site so that axonotmesis ensued. The animals were divided into two equal groups: one for the study of the effects of human growth hormone (hGH) and the other of triiodothyronine (T3). In all animals 14C-D-glucose a([14C]D-G) was injected iv as a tracer. The sciatic nerves from both sides were removed from all animals, divided into four equal segments and checked for radioactivity. In all cases an increased concentration of [14C]D-G appeared in the crushed nerve as compared with the intact one. GH administration caused a decrease in [14C]D-G uptake in both intact and injured nerves. T3 administration caused a significant decrease in [14C]D-G levels in the blood but did not substantially change [14C]D-G uptake in the crushed nerves as a whole. T3 administration appeared also to cause a peripheral displacement of the site of maximum [14C]D-G concentration in the injured nerve, indicating possibly an increased regeneration rate.

Effects of GABA, glycine, and sodium barbiturate on dendritic growth in vitro.

Dendritic growth and dendritic arborization of both the large neurons of the cerebral and the cerebellar cortex and the small bipolar neurons were studied in vitro under normal feeding conditions and under the influence of GABA, glycine, and sodium barbiturate. By the end of week 1 the neurons cultured in normal nutrient developed primary dendritic shafts, demonstrating a tendency for bifurcation. By the end of week 2 the neurons appeared as numerous secondary dendritic branches studded with spines. The dendritic development and growth proceeded continuously until week 12 when no further growth and differentiation of the dendritic arborization was noted. Feeding medium enriched with GABA or glycine enhanced dendritic growth and dendritic arborization in vitro. On the contrary, feeding medium contained sodium barbiturate, partially suppressed dendritic growth and dendritic arborization in the neurons of the cerebral and the cerebellar explants. Ultrastructural studies revealed that sodium barbiturate partially suppressed the synapse formation between the neuronal circuits of the cortical explants.

Effects of intracerebroventricular administration of atrial natriuretic peptide (ANP) on blood pressure, heart rate and plasma ADH and corticosterone levels in normal and dehydrated rabbits.

In order to investigate the effects of centrally administered Atrial Natriuretic Peptide (ANP) on plasma ADH and corticosterone levels as well as on blood pressure and on heart rate, 20 male New Zealand White (NZW) rabbits were used. Measurements were made on restrained conscious animals one week after the implantation of an indwelling intracerebroventricular (i.c.v.) cannula and two indwelling intravascular catheters (intracarotid and intrajugular). Animals were classified into two main groups, those with water available ad libitum ("euhydrated" group) and those who were dehydrated for 24h ("dehydrated" group) before blood pressure and heart rate recordings and blood sampling for hormonal determination. Each group's individuals were divided into two subgroups of five animals each. Blood samples were collected at 0 min (control) and 30; 60, 90, 120 min following i.c.v. administration of 25 microliters of either artificial cerebrospinal fluid (aCSF) (subgroups "aCSF") or human (h) ANP (1 microgram) in aCSF (25 microliters) (subgroups "hANP"). Blood pressure and heart rate were also recorded at the same times. Plasma ADH and corticosterone concentrations were determined by RIA. The results were analysed by ANOVA. Blood pressure and heart rate values were unaffected by water deprivation or by ANP administration. Mean plasma corticosterone levels at all times (30-120 min) were significantly higher (p < 0.001) than at 0 min time. Plasma corticosterone levels in the "dehydrated + aCSF" group were significantly higher (p < 0.05) than in each of the other groups ("dehydrated + hANP", "euhydrated + aCSF", "euhydrated + hANP"). Plasma corticosterone levels in each of those other groups did not differ significantly from one another. Dehydration resulted in an increase in ADH levels (p < 0.0001) and i.c.v. administration of hANP prevented (p < 0.05) in "dehydrated + hANP" experimental group, the increase in ADH levels observed in the control "dehydrated + aCSF" group from 90 to 120 min. The increase of corticosterone and ADH in the control dehydrated groups could possibly be due to the combined stress stimulus of dehydration and restriction in the restrain box. These results indicate that centrally administered ANP, at the concentration achieved in the present study, neither affects blood pressure and heart rate in conscious restrained euhydrated and 24h-dehydrated NZW rabbits nor decreases the ADH and corticosterone response to dehydration, but does apparently modulate ADH and corticosterone responses to other stimuli in the dehydrated state. In conclusion, the results of this study confirm that brain ANP may have an inhibitory effect on stimulated ADH and corticosterone release.