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Biomedical subjects

L Calza

Publications and source records attributed to L Calza.

At least 19 recordsLinked to original sources

Inhibin subunits in human placenta: localization and messenger ribonucleic acid levels during pregnancy.

This study describes the difference in distribution and levels of inhibin alpha, beta A- and beta B-subunit messenger ribonucleic acids in human placenta during pregnancy. Northern blot analysis indicated that inhibin alpha messenger ribonucleic acid is present in placental extracts collected at the early stage of gestation. Hybridization to inhibin beta A messenger ribonucleic acid was detected in the first trimester but in much lower levels. However, the intensity of the hybridization signal for inhibin alpha- and beta A-subunit messenger ribonucleic acids was greater in extracts prepared from term placentas than in those from the first or second trimester of pregnancy. Low levels of inhibin beta B-subunit messenger ribonucleic acid were observed only in extracts prepared from term placenta. At both early stage and term gestation trophoblast cells showed a positive fluorescent signal with the inhibin alpha-, beta A- and beta B-subunit-specific antisera. However, whereas inhibin alpha-subunit was localized in the cytotrophoblast, inhibin beta B-subunit immunoreactivity was observed in the syncytial layer of the villi, and inhibin beta A-subunit was widely distributed. The different distribution of immunoreactive inhibin subunits was confirmed by in situ hybridization, showing the different localizations of the inhibin messenger ribonucleic acids. These results showed that (1) human placenta produces the inhibin alpha- and beta A-subunits as early as the first trimester of pregnancy, (2) messenger ribonucleic acid levels for each of the three inhibin subunits are highest at term, and (3) immunoreactive inhibin subunits are localized differently in placental villi.

Female

Corticotropin-releasing factor and parturition: plasma and amniotic fluid levels and placental binding sites.

We evaluated levels of corticotropin-releasing factor in the plasma and amniotic fluid of women who had spontaneous vaginal delivery or elective cesarean. Corticotropin-releasing factor binding sites were also studied in placental tissue collected from vaginal or cesarean birth. Plasma samples were collected hourly from seven women from the onset of labor until delivery, and from ten women before and during elective cesarean. Amniotic fluid samples were collected from 40 women at different stages of labor and from ten women during elective cesarean. Maternal plasma corticotropin-releasing factor levels increased during labor, showing the highest values at delivery. No significant differences in amniotic fluid immunoreactive corticotropin-releasing factor levels were observed at the different stages of cervical dilatation. At cesarean, maternal plasma levels did not differ significantly from those found before surgery, and in the amniotic fluid they were similar to those found in pregnancy. The number of 125I-corticotropin-releasing factor binding sites in placental tissue was higher after vaginal than after cesarean delivery. These results suggest that corticotropin-releasing factor secretion is activated by the stress of labor.

Adult

Effects of lesions and ganglioside GM1 treatment on striatal polyamine levels and nigral DA neurons. A role of putrescine in the neurotropic activity of gangliosides.

The effects of a partial hemitransection at the meso-diencephalic level, with or without chronic ganglioside GMI treatment, have been evaluated on striatal polyamine levels, 7, 14 and 21 days after lesion, as well as on the ability of the polyamine synthesis inhibitor alpha-difluoromethylornithine (alpha-DFMO) to modulate the protective effects of chronic ganglioside GMI treatment against retrograde degeneration of the nigral dopamine (DA) nerve cell bodies (14 day time interval). The striatal polyamine levels were measured by high pressure liquid chromatography after dansylation of the polyamines. The nigral DA nerve cells were studied by means of tyrosine hydroxylase (TH) immunocytochemistry using the indirect immunoperoxidase technique. Quantitation was performed by means of morphometrical evaluation of the TH immunoreactive area of the substantia nigra. Seven days after partial hemitransection there is a marked increase (above 350%) in striatal putrescine levels, which is not modulated by chronic GMI treatment. This marked increase could, to a large extent, be counteracted by simultaneous treatment with alpha-DFMO, which blocks mainly the synthesis of putrescine. Twenty-one days after lesion chronic GMI treatment could produce an increase in striatal putrescine levels on the intact side and also after this time-interval prevent the reduction of striatal spermine levels. It was also found that simultaneous treatment with alpha-DFMO prevents the development of the protective action of chronic ganglioside GMI treatment against retrograde degeneration of the nigral DA neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Evidence for cholecystokinin-dopamine receptor interactions in the central nervous system of the adult and old rat. Studies on their functional meaning.

Evidence has been presented for the existence of interactions between CCK and DA receptors both in striatal and limbic membranes. A similar type of modulation by CCK-8 of DA receptors also exists after chronic neuroleptic treatment indicating that supersensitive DA receptors are also modulated by this peptide. As seen from simulation curves, CCK-8 increases the binding of [3H]DA agonists and reduces the binding of [3H]DA antagonists in striatal membranes, suggesting that CCK-8 may increase striatal DA transmission. Results of this type may underlie some of the non-neuroleptic effects of CCK-8. In the aged brain, the ability of CCK-8 to modulate DA antagonist binding sites is changed such that the binding of [3H]DA antagonists is increased. Thus, in the aged brain, receptor-receptor interactions may be altered, leading to a derangement of heterostatic mechanisms (mechanisms changing chemical transmission without interfering with synaptic homeostasis). It was also demonstrated that during aging there is a preferential disappearance of CCK-like immunoreactivity versus TH immunoreactivity in the nigral DA neurons, especially in the medially located nigral DA cells; furthermore, co-existence in the TH/CCK co-storing terminals in the nucleus accumbens was reduced during aging. Such alterations should also lead to changes in heterostatic regulation because the CCK co-modulation line controlling the DA receptors may be preferentially affected.

Aging

Effects of gangliosides on the functional recovery of damaged brain.

The effect of GM1 ganglioside on the recovery of dopaminergic nigro-striatal neurons was studied in rats after unilateral hemitransection. GM1 treatment favoured the collateral sprouting of dopaminergic axons in the striatum as indicated by the induced increase of tyrosine hydroxylase (TH) activity and immunofluorescence. Concomitantly GM1 partially prevented the decrease of TH activity caused by the hemitransection in the substantia nigra ipsilateral to the lesion. A significant increase of TH immunoreactivity was also detected in the substantia nigra: GM1 prevented the disappearance of TH-positive cell bodies and increased the formation of TH-positive collaterals and dendrites with respect to the saline treatment. The addition of GM1 to embryonic dissociated mesencephalic cell cultures stimulates the expression of dopaminergic characteristics as suggested by the increase of 3H-DA uptake.

Animals

A method for rostrocaudal integration of morphometric information from transmitter-identified cell groups. A morphometrical identification and description of 5-HT cell groups in the medulla oblongata of the rat.

A method has been developed to integrate rostrocaudal information from morphometrically characterized 5-HT nerve cell groups visualized by means of the indirect immunofluorescence technique in single coronal sections of the neuroaxis. The present method has been applied to the 5-HT positive cells of the medulla oblongata of the rat. 5-HT cell body and cell group parameters were measured by the use of a semiautomatic image analyzer (Kontron, MOP AMO 2) plugged into an Apple II computer. The density distribution of 5-HT positive cells was also studied by dividing the area analyzed into unitary squares (about 120 X 120 micron) and then by considering the number of 5-HT cells falling in each of these squares. The existence of a 5-HT cell group was determined by testing the randomness of the 5-HT profiles per unitary square. The entire population of 5-HT positive cells as well as the 5-HT cell groups were described in terms of gravity center coordinates, mean maximal diameter and homogeneity index. A rostrocaudal representation of the gravity centers and of the dispersion of the 5-HT nerve cell groups around them provided an exact three-dimensional description of the respective locations of the 5-HT cell groups within the medulla oblongata. These methods can be applied to all types of transmitter-identified cell groups and at any level of the neuroaxis.

Animals

Studies on aging processes.

By means of computer assisted morphometry and microdensitometry it has been possible to characterize aging processes in transmitter identified neurons demonstrated at the presynaptic level by immunocytochemistry and at the postsynaptic level by receptor autoradiography. Three-month- and 24-month-old rats were used in the present study. It was discovered that the DA neurons innervating the striatum and nucleus accumbens underwent degeneration in the aging brain both at the pre- and post-synaptic level, while the DA synapses within the tuberculum olfactorium remained intact. In this quantitative receptor autoradiographical analysis 3H-spiperone and 3H-N-propyl-norapomorphine were used as radioligands for DA receptors. In comparison with the aging induced changes in DA receptors in the striatum and in the nucleus accumbens the alpha 2- and the beta-adrenergic receptors appeared to be more resistant to the aging process. In the analysis of the opiate receptors of the aging brain it could be demonstrated by quantitative receptor autoradiography using both radioligands for the mu-type (3H-etorphin) and delta-type (3H-d-ala2-d-leu5-enkephalin) of opiate receptors that there is a marked and widespread disappearance of both types of opiate receptors in the aging brain. It must be emphasized that no correlation exists in the degeneration pattern of the mu- and delta-type of opioid receptors indicating that they may represent two separate entities with separate trophic regulation. In contrast, it was discovered in the quantitative receptor autoradiographical analysis that 3H-flunitrazepam binding was increased in many areas of the aging brain compared with the adult rat brain. These results underline the heterogeneity in the degenerative patterns which take place in transmitter receptors in relation to aging. Thus, these results indicate that the simple replacement therapy in aged patients may not give optimal results. As a matter of fact, such treatments can lead to a further unbalance between the various types of transmitter identified neurons building up the neuronal networks of the brain, which are undergoing degeneration.

Aging

Further studies on the effects of the GM1 ganglioside on the degenerative and regenerative features of mesostriatal dopamine neurons.

By means of computer assisted morphometry and microdensitometry the effects of chronic GM-1 ganglioside treatment have been further evaluated on the degenerative and regenerative features of mesostriatal DA neurons in the rat brain. In this study mainly a rostrocaudal morphometrical analysis was performed in the substantia nigra of the lesioned side. The specificity of the action of the GM-1 ganglioside on the substantia nigra DA cells was evaluated by a comparison with antiinflammatory drugs such as betametazon and acetylsalicylic acid. In the rostrocaudal analysis it was demonstrated that chronic GM-1 treatment preferentially protected the caudally located dopamine nerve cells from degeneration after partial hemitransection, while instead this chronic GM-1 treatment increased tyrosine hydroxylase immunoreactivity mainly within the rostrally located DA nerve cells present close to the site of the lesion. Furthermore, the specificity of the GM-1 action was demonstrated by the absence of protective effects of chronic treatment with betametazon and acetylsalicylic acid on the dopamine nerve cells of the lesioned side. These results open up the possibility that chronic GM-1 treatment, by exerting a stimulatory metabolic action on the DA nerve cells located close to the lesion, can enhance the production of neurotrophic factors in these cells, which in turn can diffuse out to increase the survival of the less severely lesioned DA nerve cells located in the caudal part of the substantia nigra. These results indicate that chronic GM-1 treatment may be beneficial in the treatment of neurons undergoing degeneration, which takes place e.g. in Parkinson's disease and after mechanical injury to the brain due to accidents or neurosurgical operations.

Animals

Morphometrical analysis of the distribution of luteinizing hormone-releasing hormone and tyrosine hydroxylase-immunoreactive nerve terminals within the lateral palisade zone of the median eminence of the male rat.

By means of a semiautomatic image analyzer coupled to an Apple II computer with suitable computer programs it has been possible to demonstrate in a quantitative way the morphological interaction between luteinizing hormone-releasing hormone (LH-RH) and tyrosine hydroxylase (TH)-immunoreactive nerve terminals in the lateral palisade zone (LPZ) at various rostrocaudal levels of the median eminence. The overlap area represented about 50% of the TH- or the LH-RH-immunoreactive area. The dopamine nerve terminals showed a more medial and ventral position than the LH-RH-immunoreactive nerve terminals. The transmitter-identified nerve terminals in the LPZ may be organized in strips extending in the rostrocaudal direction and may have a differential regulation.

Animals

Quantitative autoradiographic localization of [3H]imipramine binding sites in the brain of the rat: relationship to ascending 5-hydroxytryptamine neuron systems.

Quantitative autoradiography shows that there is a close relationship between [3H]imipramine binding sites and the distribution of 5-hydroxytryptamine (5-HT) neurons in the rat brain. High labeling is observed in the midbrain raphe nuclei, the areas of the dopamine cell groups of the substantia nigra and of the ventral tegmental area of Tsai, the ventral amygdaloid nucleus, the midline thalamic area, and parts of the hypothalmus. Thus, antidepressant drugs that have high affinity for [3H]imipramine binding sites can exert an influence at the 5-HT cell body as well as at the 5-HT nerve terminal level. The present results underline the possibility that the 5-HT and dopamine hypotheses for the mechanism of action of antidepressant drugs are not mutually exclusive, because both 5-HT and dopamine neurons can be regulated by large numbers of [3H]imipramine binding sites.

Animals

Chronic treatment with 1-dopa plus carbidopa in hemitransected rats: preferential effects at intact dopamine synapses leading to behavioural signs of dopamine receptor supersensitivity.

Chronic i.p. treatment with 1-dopa-carbidopa for 3 weeks in hemitransected male rats leads on one hand to tolerance to 1-dopa induced turning behaviour and on the other hand to behavioural and biochemical signs of dopamine (DA receptor supersensitivity on the intact side. Thus, the apomorphine induced ipsilateral turning behaviour is enhanced and the KD values of the 3H-spiperone binding sites linked to DA receptors of the D2 type on the intact, but not on the denervated side are reduced by 40%. However, the number of 3H-spiperone binding sites is reduced by 20% in striatal membranes on the intact side after this type of treatment. Therefore, chronic treatment with a catecholamine (CA) precursor leads to selective adaptive changes at intact striatal DA synapses with certain signs of the expected development of DA receptor subsensitivity, but above all with signs of paradoxical development of DA receptor supersensitivity. A hypothesis is introduced to explain these results.

Animals

Gangliosides increase the survival of lesioned nigral dopamine neurons and favour the recovery of dopaminergic synaptic function in striatum of rats by collateral sprouting.

The effects of chronic ganglioside treatment GM-1 (10 mg/kg, i.p., once daily for 56 days) have been evaluated on the degenerative and regenerative features of nigrostriatal dopamine (DA) neurons following a partial lesion by tyrosine hydroxylase immunocytochemistry in combination with morphometrical analysis and by quantitative DA receptor autoradiography. Chronic GM-1 treatment resulted in the maintenance in the number of DA cell bodies, terminals and striatal area on the lesioned side and also increased dendrite length of the DA nerve cells in the zona reticulata on that side. The lesion induced DA receptor supersensitivity was counteracted by chronic treatment with GM-1 and the apomorphine induced rotational behaviour was significantly reduced. The hypothesis is introduced that following ganglioside treatment some lesioned DA nerve cells do not degenerate, but elongate their dendrites to give increased trophic support to DA cell bodies with intact DA axons. These increased dendro-dendritic interactions may enable the unlesioned DA cells to increase the density of their striatal nerve terminal networks via collateral sprouting leading to recovery of dopaminergic synaptic function as evidenced in the receptor autoradiographical and behavioural analysis. Gangliosides may therefore possibly represent a new type of drug in the treatment of Parkinson's disease and aging processes in DA systems.

Animals

A new approach to quantitate the density and antigen contents of high densities of transmitter-identified terminals. Immunocytochemical studies on different types of tyrosine hydroxylase immunoreactive nerve terminals in nucleus caudatus putamen of the rat.

By means of a semi-automatic image analyzer plugged into an Apple II computer and suitable computer programs it is possible to analyze transmitter-identified nerve terminals. Thus, a densitometric approach is applied on the original photograph followed by systematic sampling which is carried out by means of a grating of circles. This procedure allows the study quantitatively of density and intensities of different types of densely packed tyrosine hydroxylase (TH) immunoreactive nerve terminals of the nuc. caudatus putamen. It is shown that the islandic TH immunoreactive nerve terminals have a higher density, but a TH content similar to the diffuse types of TH immunoreactive nerve terminals in the nuc. caudatus putamen.

Animals