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Biomedical subjects

P F Spano

Publications and source records attributed to P F Spano.

At least 19 recordsLinked to original sources
PubMed1995

Tau protein immunolocalization in fetal and adult human spinal cord.

In the present study, the monoclonal antibody Alz-50 has been used to determine and compare the immunohistochemical localization of phosphorylated tau proteins in the developing and normal adult spinal cord. At all stages of fetal life Alz-50 fiber immunoreactivity was observed in the dorsal roots, in the dorsal and dorsolateral funiculi, and in restricted regions of the dorsal horn. Alz-50 immunoreactivity was also demonstrated in the dorsal root ganglion neurons. In the adult spinal cord a consistent pattern of Alz-50 fiber immunoreactivity was localized in the superficial layers of the dorsal horn (lamina I and II) but not in dorsal and dorsolateral funiculi and in the dorsal root ganglion. Comparable results in fetal specimens have been obtained employing PHF-1, a monoclonal antibody generated against paired helical filament proteins from Alzheimer brains, while no significant immunostaining for PHF-1 was observed in the adult spinal cord. In addition, the staining with monoclonal and polyclonal anti-tau antibodies overlapped with that of Alz-50. The transient, selective pattern of Alz-50 and PHF-1 immunoreactivity may disclose some relevant functions of tau proteins during somatosensory pathway development.

Adult↗
PubMed1995

Dopaminergic drugs in congestive heart failure: hemodynamic and neuroendocrine responses to ibopamine, dopamine, and dihydroergotoxine.

Ibopamine has hemodynamic and neurohumoral effects potentially useful for the treatment of congestive heart failure (CHF), but its mechanism of action is not completely clear. To evaluate the role of dopaminergic receptor stimulation in the hemodynamic and neurohumoral activity of ibopamine, we compared the effects of ibopamine, 100 mg orally (p.o.) with those of the dopamine 2, 4, and 6 micrograms/kg/min intravenously (i.v.) and of the DA2 agonist dihydroergotoxine 6 micrograms/kg i.v. in 13 patients with chronic CHF [left ventricular ejection fraction (LVEF) < or = 35%]. All patients underwent right heart Swan-Ganz catheterization with determination of hemodynamic parameters at baseline, after 30 min of infusion of each dose of dopamine (DA) and < or = 6 h after ibopamine and dihydroergotoxine administration. Blood samples for the assessment of plasma renin activity (PRA), aldosterone, norepinephrine (NE), and epinephrine (Epi) were also obtained. Ibopamine induced a peak 21% increase of cardiac index (CI) with a 23 and 25% increase in stroke volume (SV) and stroke work indexes (SWI), respectively, and an 18% reduction in systemic vascular resistance (SVR). Similar changes were observed after DA infused at the doses of 2 and 4 micrograms/kg/min, whereas with the dose of 6 micrograms/kg/min heart rate (HR) increased by 23% and SV index (SVI) did not change further. Dihydroergotoxine administration induced only a significant 9% decrease in mean arterial pressure (MAP), with a 13% reduction in SVR.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate and kainate differently affect neuronal cytoarchitecture of rat cerebellar granule cells.

Rat cerebellar granule cells cultured in media containing 12 mM KCl showed short life-span, did not branch, and died after 10 days in vitro. The cell exposure to N-methyl-D-aspartate (NMDA) or to kainate promoted both neuron survival and branching, reproducing the viability and the neurite extension routinely observed in cultures maintained in media containing 25 mM KCl. Exposure of neurons to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) resulted in an increased survival not associated with neuritic arborization. These results suggest that the glutamate ionotropic receptor subtypes differently contribute in elaborating neuronal morphogenesis.

Animals↗
PubMed1994

Antisense strategy unravels tau proteins as molecular risk factors for glutamate-induced neurodegeneration.

1. We investigated the possible involvement of tau proteins in the neurotoxic process activated by glutamate using the oligonucleotide antisense strategy. 2. We found that pretreatment of granule cells with an antisense oligonucleotide of the tau gene completely prevented the increase in tau immunoreactivity induced by glutamate. 3. A significant amount of the tau antisense oligonucleotide (about 1 to 2% of total) was taken up by the cells and remained stable in the cells for at least 60 min. A dose-response study revealed that 25 microM tau antisense oligonucleotide was the most efficacious concentration in terms of prevention of glutamate-induced tau immunoreactivity increases, without affecting basal tau expression. Higher concentrations of tau oligonucleotide antisense reduced tau immunoreactivity in control cells. 4. Significantly, the concentration-response curve of glutamate for inducing neuronal death in cells pretreated with tau antisense oligonucleotide showed a shift to the right compared to those obtained in untreated or tau sense oligonucleotide-treated cells. 5. Since inhibition of tau synthesis does not completely prevent but only decreases the neuronal sensitivity to glutamate, it is tempting to speculate that accumulation of tau within the neuron in response to glutamate represents one of the molecular risk factors lowering the safety margin of neurons to excitotoxic-induced injury.

Animals↗
PubMed1993

Deafferentation induces early and delayed differential changes in the pattern of expression of the various guanine nucleotide binding protein mRNAs in rat striatum.

A polymerase chain reaction-derived method was used to identify and quantitate the relative abundance of the different mRNAs encoding various isoforms of the guanine nucleotide regulatory protein Gs, Gi, and Go alpha subunits in the striata of rats unilaterally injected with 6-hydroxydopamine in the substantia nigra. Thirty days after the lesion, the mRNA levels of the G(o) and of the Gi 1 alpha subunits were increased by about 2-3 times, those of the Gi 3 decreased by about 60% and those of Gi 2 and Gs unmodified. The pattern of expression of the G(o) alpha subunits mRNA changed in a time-dependent fashion, being significant 20 days after the lesion. The decrease in Gi 3 alpha subunit mRNA levels was maximum 10 days after the lesion and tended to be reduced in magnitude with time while the changes in Gi 1 alpha subunit mRNA showed a byphasic behaviour being reduced at 10 days and increased at 30 days after the lesion. These data suggest that the expression of the various G protein alpha subunits in the striatum are continuously regulated by factors originating from afferent neurons and surrounding cells.

Animals↗
PubMed1992

Requirement of oestrogens for the sensitivity of prolactin cells to vasoactive intestinal peptide in rats and man.

Vasoactive intestinal peptide (VIP) is a prolactin-releasing hormone which is involved in the multifactorial modulation of prolactin secretion in mammals. Intravenous injection of VIP (1 microgram/kg) to fertile women increased plasma prolactin levels and heart rate and reduced diastolic pressure. The same treatment to menopausal women caused similar cardiovascular effects but did not modify plasma prolactin levels. In contrast, TRH (200 micrograms, i.v.) induced a significant increase in plasma prolactin levels in both fertile and menopausal women. The relevance of oestrogens in affecting VIP-stimulated prolactin secretion was evaluated in vitro by measuring prolactin release from pituitary cells of control and ovariectomized rats. The sensitivity of rat mammotrophs to VIP, but not to TRH, was completely suppressed 3 or 4 weeks after ovariectomy. Furthermore, implantation of rats with a silastic capsule containing oestradiol-17 beta during ovariectomy, preserved the cell responsiveness to VIP. The prolactin-releasing property of VIP was also restored when pituitary cells from ovariectomized rats were cultured for 3 days in the presence of 10 nmol oestradiol-17 beta/l before being used for prolactin release experiments. The present study shows that the ability of prolactin-secreting cells to respond to the stimulatory action of VIP requires high levels of circulating oestrogens, both in man and rats.

Adult↗
PubMed1990

Repeated administration of lisuride down-regulates dopamine D-2 receptor function in mesostriatal and in mesolimbocortical rat brain regions.

Functional modifications of both D-1 and D-2 dopamine (DA) receptor subtypes following repeated administration of lisuride, a DA agonist that acts selectively on D-2 DA receptors were studied. The functional state of D-1 and D-2 DA receptors was evaluated from measurements of SKF 82526-stimulated and bromocriptine-inhibited adenylate cyclase activity in different brain regions of rats treated daily for 26 days with saline or lisuride (100 micrograms/kg i.p.). Persistent stimulation by lisuride of DA receptors in striatum, nucleus accumbens, substantia nigra, frontal cortex, hippocampus and pituitary gland induced a down-regulation of D-2 receptors without changing the functional activity of D-1 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Dopaminergic regulation of aldosterone secretion. Biochemical mechanisms and pharmacology.

Aldosterone secretion is subject to both stimulatory and inhibitory controls. Angiotensin II (AII) is the primary regulator of aldosterone production and an inhibitory role of dopamine (DA) has been suggested recently. We have reported that two different DA receptors are present in rat adrenal glomerulosa: D-1, associated with stimulation of adenylate cyclase, and D-2, coupled in an inhibitory way with the cyclic AMP (cAMP) generating system. By measuring aldosterone secretion and cAMP formation in intact adrenal glomerulosa cells, we also found a specific functional interaction between D-2 receptors apparently associated with inhibition of cAMP formation and AII in the regulation of aldosterone production.

Adrenal Glands↗
PubMed1990

Beta 1- and beta 2-receptors are differentially desensitized in an experimental model of heart failure.

Recent reports suggested that a complex alteration in beta-receptor function occurs in failing human myocardium. We evaluated beta-receptor-subtype activity in an experimental model of monocrotaline (MCT)-induced cardiomyopathy in the rat. Through pulmonary hypertension, MCT causes right ventricular hypertrophy (RVH), either associated with heart failure or not, beta-Receptor function was evaluated in both failing-hypertrophic and hypertrophic hearts in binding studies with [125I]iodocyanopindolol (ICYP) and by measuring adenylate cyclase (AC) activity. In the right failing ventricle, beta 1- but not beta 2-receptor density was decreased. Lesion-associated modifications in the adenylate cyclase system were also observed: isoproterenol- and guanosine 5' [beta, gamma-imido]triphosphate [Gpp(NH)p]-stimulated cyclic AMP formation was reduced in the right failing ventricle, while the cyclic AMP responses to NaF and forskolin were unchanged. On the other hand, no changes in either beta-receptor density or function were found in hypertrophic ventricles. MCT-induced heart failure in the rat is thus associated with a selective decrease of beta 1-receptor density and function. These results suggest that MCT-induced cardiac failure may be an appropriate model in which to investigate heart insufficiency further.

Adenylyl Cyclases↗
PubMed1990

A mechanism additional to cyclic AMP accumulation for vasoactive intestinal peptide-induced prolactin release.

Vasoactive intestinal peptide (VIP) is a prolactin (PRL)-releasing factor which has been proposed to exert its secreting property by activating the adenylate cyclase enzyme. The present study shows that the omission of external Ca2+ did not affect the ability of VIP to induce PRL release while it completely abolished the VIP stimulatory effect on adenylate cyclase. We found that VIP (500 nM) stimulated PRL secretion in a time-dependent manner reaching a plateau at 3 min. This pattern was not changed when Ca2+ was omitted from the incubation medium. When tested at different concentrations, VIP stimulated PRL release with EC50 values of 1.3 nM in the presence of Ca2+ and 30 nM in the absence of Ca2+. On the other hand, Ca2+ removal completely suppressed the VIP-induced cAMP formation. VIP (200 nM) was also found to activate Ca2+ influx into pituitary cells. The increase in Ca2+ permeability showed a peak at 5 s and remained significantly higher than control values until 1 min. In conclusion, in an experimental condition where Ca2+ was omitted from the medium, VIP was found to induce PRL release without stimulating cAMP production. This cAMP-independent PRL release was blocked by preincubation of the cells with 1 microgram/ml pertussis toxin. An additional mechanism other than adenylate cyclase activation or Ca2+ entry is proposed to sustain VIP-induced PRL release.

Adenylate Cyclase Toxin↗
PubMed1990

[The adrenergic beta system in an experimental model of heart failure].

Reports in the literature have suggested that a complex alteration in beta-receptor pathway takes place in failing human myocardium. The purpose of our study was to evaluate the beta-adrenergic receptor system in an experimental model of heart failure induced by monocrotaline in rats. Monocrotaline, administered with a single intraperitoneal injection (50 mg/Kg), causes pulmonary hypertension and right ventricular hypertrophy, associated with congestive heart failure. beta 1 and beta 2-receptors were characterized in the right ventricle by direct radioligand binding utilizing [125I] Iodocyanopindolol and selective beta 1-(CGP 20712A) and beta 2-(ICI 118551) antagonists. Adenylate cyclase was measured in basal condition and in the presence of different stimulators as isoproterenol with ICI 118551 (beta 1-receptor-stimulated activity), isoproterenol with CGP 20712A (beta 2-receptor-stimulated activity), Gpp(NH)p, NaF and forskolin. In the right ventricle of the failing hearts the beta 1-receptor density decreased selectively (-55.8%) while the beta 2-receptor density was unchanged. Modifications in the adenylate cyclase system were demonstrated: a reduction in the basal and beta 1- and beta 2-stimulated adenylate cyclase activity; a decrease in adenylate cyclase activation elicited by Gpp(NH)p, but not by forskolin and NaF. In conclusion, these data suggest that in monocrotaline-induced heart failure in the rat there is a selective beta 1-receptor down-regulation and an impaired coupling efficiency of G proteins. These results are in line with biochemical changes found in patients with heart failure.

Adenylyl Cyclases↗
PubMed1990

[Regulation mechanisms in prolactin secretion. Possible role of the hypophyseal renin-angiotensin system].

Recent studies have shown a possible role of different factors in the regulation of prolactin secretion. In fact many neurotransmitters (dopamine) and peptides can modulate prolactin release from anterior pituitary lactotrophs. In vitro and in vivo studies, Angiotensin II has been shown to increase prolactin release. On the basis of these data we have studied the effects of enalapril (ACE-Inhibitor) on baseline plasma prolactin in nine hypertensive post-menopausal women. The results indicate that 15-day inhibition of angiotensin-converting enzyme by enalapril significantly reduced serum prolactin levels. These data suggest that the Angiotensin II may play a role in the control of prolactin secretion in hypertensive women.

Aged↗
PubMed1989

Properties of benzodiazepine binding sites in peripheral blood lymphocytes.

Benzodiazepine (BDZ) binding sites were studied by using 3H-diazepam and 3H-Ro 5-4864 in intact lymphocytes from peripheral blood (PBL), in comparison to kidney and cerebellum. Experiments with 3H-diazepam performed at equilibrium and measuring kinetics revealed that BDZ binding sites are indeed present in rat PBL. The binding is saturable (Bmax 557 fmoles/10(6) cells), with high affinity (KD = 9.3 nM) and reversible. Specific binding sites are also observed by saturation experiments with 3H-Ro 5-4864 (Bmax 175 fmoles/10(6) cells, KD 2.2 nM). In addition, analysis of saturation isotherms obtained with 3H-diazepam indicates that BDZ binding sites are also present in human PBL. Scatchard plot of binding isotherms revealed an apparent single population of sites in all cases. The pharmacological characterization of BDZ binding sites in PBL, as compared with those of kidney and cerebellum, showed that these sites belong to the so-called "peripheral type."

Animals↗