Neuroprotective effect of treatment with calcium antagonists on hypertensive retina.

The influence of hypertension and of treatment with the dihydropyridine-type Ca2+ antagonists lercanidipine, manidipine, nicardipine, and nimodipine and with non dihydropyridine-type vasodilator hydralazine on retinal nervous and glial fibrillary acidic protein (GFAP) immunoreactive astrocytes were investigated in male spontaneously hypertensive rats (SHR). Normotensive Wistar-Kyoto (WKY) were used as normotensive references group. Treatment of animals with oral equi-hypotensive doses of the above compounds started at 14 weeks of age and lasted for 12 weeks.

Neuronal populations of rat cerebral cortex and hippocampus expressed a higher density of L-type Ca 2+ channel than corresponding cerebral vessels.

Dihydropyridine (DHP)-type Ca2+ antagonists block primarily L-type Ca2+ channels and are used in the therapy of hypertension. They were also proposed for the treatment of several central nervous system disorders. In brain, these compounds bind both neuronal and vascular Ca2+ channels, but no studies have evaluated comparatively their density at neuronal and vascular level.

The cholinergic approach for the treatment of vascular dementia: evidence from pre-clinical and clinical studies.

The involvement of an impaired cholinergic neurotransmission in the pathophysiology of cognitive impairment occurring in vascular dementia (VaD), as well as the possibility of treating it by stimulating cholinergic neurotransmission was reviewed. Pre-clinical data suggest that similarly as documented in dementia disorders of neurodegenerative origin, a cholinergic deficit is involved in the pathophysiology of cognitive impairment of vascular origin. In the past, clinical trials have evaluated cholinergic precursors such as lecithin, citicoline and choline alphoscerate.

The peripheral dopaminergic system: morphological analysis, functional and clinical applications.

In vivo administration or in vitro application of dopamine or of dopamine receptor agonists induce vasodilatation in the cerebral, coronary, renal and mesenteric vascular beds and cause hypotension. Moreover, dopamine stimulates cardiac contractility and induces diuresis and natriuresis. Peripheral (cardiovascular and renal) dopamine receptors belong to the D1-like and D2-like receptor superfamilies, thought to be located post-junctionally and pre-junctionally respectively.

Immunochemical and immunocytochemical characterization of cholinergic markers in human peripheral blood lymphocytes.

Cholinergic markers and the expression of M(2)-M(5) muscarinic cholinergic receptor subtypes were investigated in human peripheral blood lymphocytes by Western blot analysis and immunocytochemistry. The totality of peripheral blood lymphocytes express acetylcholine (ACh) immunoreactivity, choline acetyltransferase (ChAT), acetylcholinesterase (AChE), vesicular ACh transporter (VAChT) and M(2)-M(5) muscarinic cholinergic receptor protein immunoreactivity. Western blot analysis performed independently on T and B lymphocytes using anti-ChAT and anti-AChE antibodies revealed labelling of single bands of approximately 68-70 and 70 kDa, respectively, whereas VAChT was bound to two bands of approximately 80 and 45 kDa.

Protective effect of anti-hypertensive treatment on cognitive function in essential hypertension: analysis of published clinical data.

Hypertension is a risk factor for stroke and may also contribute to the development of vascular cognitive impairment (VCI) and vascular dementia (VaD). Cognitive complications of hypertension and the influence of anti-hypertensive treatment were underestimated until recently. In this paper, trials investigating the effect of anti-hypertensive treatment on cognitive function were evaluated.

Expression of peripheral blood lymphocyte muscarinic cholinergic receptor subtypes in airway hyperresponsiveness.

The expression of muscarinic cholinergic receptor subtypes was investigated in peripheral blood lymphocytes (PBL) of bronchial asthma patients by a combined kinetic and equilibrium labeling technique for radioligand binding assay of muscarinic cholinergic receptor subtypes and by receptor immunochemistry and immunocytochemistry. An increased expression of M2 and to a lesser extent of M5 receptors and no changes of M4 receptor were observed in PBL of asthmatics compared to control individuals. The increase was related to bronchial hyperresponsiveness detected by methacholine challenge test.

Dopamine D4 receptor expression in rat kidney: evidence for pre- and postjunctional localization.

Dopamine D4 receptors mediate inhibition of vasopressin-dependent sodium reabsorption by dopamine in collecting tubules. At present, the distribution of D4 receptors in other renal districts remains an open issue. The renal distribution of D4 receptor was assessed in normally innervated and denervated male Sprague-Dawley rats by quantitative immunohistochemistry using an anti-dopamine D4 receptor rabbit polyclonal antibody.

Neurotransmitter receptor expression by peripheral mononuclear cells: possible marker of neuronal damage by exposure to radiations.

Peripheral mononuclear cells (PMC) express several neurotransmitter systems. Increasing evidence suggests that PMC neurotransmitter receptors are involved in modulating immune responses. It is also thought that expression of PMC neurotransmitter receptors may reflect the status of homologous brain receptors.

Age-related changes of dopamine receptor protein immunoreactivity in the rat mesenteric vascular tree.

Dopamine D1-D5 receptor protein immunoreactivity and tyrosine hydroxylase (TH) immunoreactivity were investigated on the mesenteric arterial tree by immunohistochemistry. The density of various dopamine receptors and TH immunoreactivity was compared between young (6-month-old), adult (15-month-old) and senescent (24-month-old) Fischer 344 rats by computer-assisted microdensitometry. The dopamine D1-like (D1 and D5) receptors were localized on the tunica media of different sized mesenteric artery branches.

Muscarinic cholinergic receptor subtypes in the hippocampus of aged rats.

In spite of the suggestion of impaired muscarinic function in adult-onset cognitive disorders, data on the expression of muscarinic receptors in the hippocampus as a function of age are inconsistent. One reason may be that the majority of investigations were unable to differentiate the five brain muscarinic receptors subtypes. In this study, using a protocol based on a combination of both kinetic and equilibrium binding approaches, we have assessed the expression and the density of M1-M5 muscarinic cholinergic receptors in the hippocampus of Fisher 344 rats aged 6, 15 and 22 months.

Glial fibrillary acidic protein immunoreactive astrocytes in developing rat hippocampus.

The developmental pattern of glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes was investigated in the hippocampus (subfields CA1, CA3 and CA4) and in the dentate gyrus of male and female rats aged 11, 16, 30, 90 and 150 days by immunohistochemistry associated with image analysis. Analysis was centred on stratum radiatum, a hippocampal area rich in GFAP-immunoreactive astrocytes. The volume of different portions of hippocampus, the number and the size of astrocytes, the intensity of cell body GFAP immunostaining as well as the extension of astrocyte were assessed.

Activities of the International Radio Medical Centre (C.I.R.M.) in Rome during the last five years (1996-2000). Centro Internazionale Radio Medico.

This paper reviews medical activity provided from 1996 to 2000 by the International Radio Medical Centre (Centro Internazionale Radio Medico, C.I.R.

Effects of dihydropyridine-type Ca2+ antagonists on the renal arterial tree in spontaneously hypertensive rats.

The effects of hypertension and of treatment with dihydropyridine-type Ca2+ antagonists and the vasodilator hydralazine on renal arterial tree were investigated in spontaneously hypertensive rats (SHR) with quantitative microanatomical techniques. Pharmacological treatment decreased to a similar extent systolic blood pressure values in SHR. Increased thickness of the tunica media of intrarenal arteries accompanied and luminal narrowing were observed in control SHR.

Peripheral blood lymphocytes muscarinic cholinergic receptor subtypes in Alzheimer's disease: a marker of cholinergic dysfunction?

Muscarinic M2-M5 muscarinic cholinergic receptors were investigated in peripheral blood lymphocytes of patients with mild cognitive impairment of the Alzheimer's type (MCIAT), probable Alzheimer's disease (AD) and probable vascular dementia (VaD). [3H]-N-methyl scopolamine (NMS) in the presence of muscarinic antagonists and Mamba venom to occlude different receptor subtypes was used as radioligand. Analysis of [3H]-NMS binding curves without receptor subtype assessment resulted in a slight decrease of receptor density in AD patients.

Neurotrophins and neurotrophin receptors in human lung cancer.

The expression of neurotrophins (NTs) and related high- and low-affinity receptors was studied in surgical samples of histologically diagnosed human tumors of the lower respiratory tract. The experiment was conducted with 30 non-small cell lung cancer specimens and in eight small cell lung cancer specimens by Western blot analysis and immunohistochemistry to assess expression and distribution of NT and NT receptor proteins in tissues examined. Immunoblots of homogenates from human tumors displayed binding of anti-nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and NT-3 antibodies as well as of anti-tyrosine-specific protein kinase (Trk) A, TrkB, and TrkC receptor antibodies, with similar migration characteristics than those displayed by human beta-NGF and proteins from rat brain.

Changes of retinal neurons and glial fibrillary acid protein immunoreactive astrocytes in spontaneously hypertensive rats.

Objective: The influence of arterial hypertension on retinal neurons and glial fibrillary acid protein (GFAP) immunoreactive astrocytes was investigated in spontaneously hypertensive rats (SHRs).

Methods: The retinas of 4- and 6-month-old SHRs and age-matched Wistar-Kyoto rats (WKY) were investigated. A group of SHRs, treated from 4 to 6 months with the hypotensive drug hydralazine, was also examined.

Alpha1-adrenergic receptor subtypes in peripheral blood lymphocytes of essential hypertensives.

Objective: The expression of alpha1-adrenergic receptor subtypes in peripheral blood lymphocytes was investigated in 28 essential hypertensive patients as well as in the peripheral blood lymphocytes and aorta of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats.

Methods: Alpha1-adrenergic receptors were quantified by radioligand binding assays, employing [3H]-prazosin as the radioligand in association with compounds displaying different degrees of selectivity for alpha1A-, alpha1B- and alpha1D-adrenergic receptor subtypes.

Results: The affinity of [3H]-prazosin binding was similar in peripheral blood lymphocytes of different stage essential hypertensive and normotensive subjects or of SHR and age-matched normotensive WKY rats as well as in the aortas of SHR and WKY rats.

Hypertensive brain damage: comparative evaluation of protective effect of treatment with dihydropyridine derivatives in spontaneously hypertensive rats.

Hypertension is the main risk factor for cerebrovascular disease including vascular dementia and control of blood pressure might protect from lesions causing cognitive impairment. The influence of anti-hypertensive treatment on hypertensive brain damage was assessed in spontaneously hypertensive rats (SHR). SHR and age-matched normotensive Wistar Kyoto (WKY) rats were treated from the 14-26th week of age with the dihydropyridine-type Ca2+ channel blockers lercanidipine, manidipine and nimodipine and as a reference with the non-dihydropyridine-type vasodilator hydralazine.

Age-related changes of dopamine receptors in the rat hippocampus: a light microscope autoradiography study.

Hippocampus is a brain region involved in learning and memory and is particularly sensitive to ageing. It is supplied with a dopaminergic innervation arising from the midbrain, which is part of the mesolimbic dopaminergic pathway. Dysfunction of the dopaminergic mesolimbic system is probably involved in the pathophysiology of psychosis and behavioural disturbances occurring in the elderly.

Choline alphoscerate in cognitive decline and in acute cerebrovascular disease: an analysis of published clinical data.

This paper has reviewed the documentation on the clinical efficacy of choline alphoscerate, a cholinergic precursor, considered as a centrally acting parasympathomimetic drug in dementia disorders and in acute cerebrovascular disease. Thirteen published clinical trials, examining in total 4054 patients, have evaluated the use of choline alphoscerate in various forms of dementia disorders of degenerative, vascular or combined origin, such as senile dementia of the Alzheimer's type (SDAT) or vascular dementia (VaD) and in acute cerebrovascular diseases, such as transitory ischemic attack (TIA) and stroke. Analysis has assessed the design of each study, in particular with respect to experimental design, number of cases, duration of treatment and tests used to evaluate drug clinical efficacy.

Treatment of cognitive dysfunction associated with Alzheimer's disease with cholinergic precursors. Ineffective treatments or inappropriate approaches?

The observations of the loss of cholinergic function in neocortex and hippocampus in Alzheimer's disease (AD) developed the hypothesis that replacement of cholinergic function may be of therapeutic benefit to AD patients. The different approaches proposed or tested included intervention with acetylcholine (ACh) precursors, stimulation of ACh release, use of muscarinic or nicotinic receptor agonists and acetylcholinesterase (AChE) or cholinesterase (ChE) inhibition. Inhibition of endogenous ACh degradation through ChE inhibitors and precursor loading were treatments more largely investigated in clinical trials.

Microanatomical changes of intracerebral arteries in spontaneously hypertensive rats: a model of cerebrovascular disease of the elderly.

Changes occurring in intracerebral arteries of 24-week-old spontaneously hypertensive rats (SHR) compared with age-matched normotensive Wistar-Kyoto (WKY) rats were assessed using microanatomical techniques associated with image analysis. Morphometric parameters investigated included arterial diameter, lumen area, wall area, and wall-to-lumen ratio. Intracerebral arteries (lumen diameter>46 microm) and arterioles (lumen diameter 46-10 microm) of frontal cortex, striatum, and hippocampus were examined.

Identification of dopamine plasma membrane and vesicular transporters in human peripheral blood lymphocytes.

Plasma membrane dopamine transporter (DAT), vesicular monoamine transporters (VMAT) type-1 and -2 and the expression of the dopaminergic markers dopamine and tyrosine hydroxylase were assessed in membranes and/or in cytospin centrifuged human peripheral blood lymphocytes. The radiolabeled DAT ligand [3H]GBR12935 was bound to peripheral lymphocytes in a manner consistent with the specific binding to a dopamine uptake system, with a dissociation constant similar to that found in striatum, but with a lower density of binding sites. On the other hand, no specific binding occurred in cerebellum used as a test tissue not expressing DAT.

Dopamine receptor immunohistochemistry in the rat choroid plexus.

1. Earlier studies have demonstrated a high density of dopamine D1-like receptor binding in the choroid plexus by light microscope autoradiography, but the dopaminergic specificity of this binding was questioned. 2.