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A Carta

Publications and source records attributed to A Carta.

At least 55 records · Page 3Linked to original sources

Modulation of dopamine D1-mediated turning behavior and striatal c-fos expression by the substantia nigra.

In order to study the possible contribution of the substantia nigra (SN) in the positive interaction between dopamine D1 receptor agonists and glutamate antagonists in unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats, the effect of the D1 agonist, SKF 38393, was studied in combination with intranigral infusions of glutamate antagonists of the NMDA (MK 801, CPP) or AMPA (NBQX) type of receptor. Local infusion into the SN of the 6-OHDA lesioned side of MK 801, CPP or NBQX at doses inducing no or minimal behavioral effects significantly increased the turning behavior and the expression of c-fos induced, in the lesioned caudate-putamen (CPu), by a parenteral administration of SKF 38393. The same result was obtained after intra-SN infusion of the GABA agonist, muscimol. High doses of MK 801, CPP or muscimol infused into the SN produced intense contralateral turning per se and induced a sparse c-fos expression in the lesioned CPu which was antagonized by parenteral administration of MK 801. The results indicate that a depression of SN pars reticulata efferent neurons potentiates D1-mediated responses and suggest that this area may play a role in the positive interaction between glutamate antagonists and D1 receptor agonists.

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

Distribution of cataract types in the Italian-American case-control study and at surgery in the Parma area.

PURPOSE: To compare the distribution of cataract types at surgery with the distribution detected in an ophthalmology clinic-based case-control study in the same geographic area (Parma, Italy). METHODS: The distribution of cataract type assessed according to the Lens Opacities Classification System I in 284 consecutive patients 45 years of age or older, who were admitted for cataract surgery to the Institute of Ophthalmology in Parma during 1994, was compared with the distribution assessed in 1008 participants in the Italian-American case-control study of age-related cataract in the Parma metropolitan area from 1987 to 1989. RESULTS: Analysis of cataract distribution indicates in the surgical group, compared with the case-control population, a significant increase of nuclear (N) and posterior subcapsular (PSC) opacities (any), a reduction of pure forms of cortical and N cataracts, and a marked increase of mixed types of opacities with a simultaneous N and PSC component. CONCLUSION: Although cortical opacities are probably the most prevalent type of age-related lens change in the general population of Parma metropolitan area, the type of cataract most frequently responsible for the decision of patients to undergo cataract surgery is a mixed type of opacity with an N-PSC component.

Aged↗

Is early-onset Alzheimer disease a distinct subgroup within the Alzheimer disease population?

Although patients with Alzheimer disease (AD) share major clinical and neurohistologic features regardless of age of onset, the hypothesis that early-onset AD comprises a distinct subgroup remains viable. Most studies addressing this hypothesis find quantitative differences between early- and late-onset AD patients. Early-onset AD is characterized by shorter survival, more rapid cognitive deterioration, greater frequency of language disturbance, more severe and widespread neurochemical abnormalities, and a greater density of neurohistologic lesions. In addition, both the chromosome 14 genetic abnormality and chromosome 21 amyloid precursor protein mutations appear restricted to early-onset familial AD. Age of onset of AD subjects may be relevant to the design of clinical trials. For example, the efficacy of a drug that slows disease progression may be more easily demonstrated in subjects with early-onset disease.

Age of Onset↗

Intranigral injections of glutamate antagonists modulate dopamine D1-mediated turning behavior and striatal c-fos expression.

The contribution of the substantia nigra (SN) in the positive interaction between dopamine D1 receptor agonists and glutamate antagonists was studied in rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of dopaminergic nigro-striatal pathway. Local infusion into the SN of the 6-OHDA lesioned side of NMDA glutamate antagonists MK 801 and CPP or the AMPA antagonist NBQX at doses inducing none or minimal behavioral effects, significantly increased the turning behavior and the expression of c-fos induced, in the lesioned caudate-putamen (CPu), by a parenteral administration of SKF 38393. High doses of MK 801 or CPP infused into the SN produced intense contralateral turning per-se but induced only sparse c-fos expression in the lesioned CPu. The results show that a depression of SN pars reticulata efferent neurons, potentiates D1-mediated responses and suggest that this area may play a role in the positive interaction between glutamate antagonists and D1 receptor agonists.

Animals↗

Differential effect of MK 801 and scopolamine on c-fos expression induced by L-dopa in the striatum of 6-hydroxydopamine lesioned rats.

In rats with a unilateral 6-hydroxydopamine lesion of the dopaminergic nigro-striatal pathway, striatal D1-receptor-stimulated c-fos expression and turning behavior are positively modulated by D2 receptor stimulation and by blockade of N-methyl-D-aspartate (NMDA) or muscarinic receptors. Combined D1/D2 receptor stimulation by L-dopa activates c-fos in a manner not additive with muscarinic receptor blockade by scopolamine. On the other hand, blockade of NMDA receptors by MK 801 reduced c-fos expression induced by L-dopa while, depending on the dose of L-dopa, differentially affecting contralateral turning behavior. The results are interpreted to suggest that D2 receptor stimulation amplifies D1-receptor-mediated c-fos expression by two mechanisms differentially related to muscarinic and NMDA receptors.

Animals↗

HLA-DRB and -DBQ typing by PCR amplification using sequence-specific primers (PCR-SSP): assessment after 1 year of routine use by three laboratories.

Using sequence-specific amplifications, a practical and fast technique for DRB and DQB typing has been developed. The primers are chosen in order to amplify groups of alleles corresponding to the same serological specificity. In a second step, precise allelic determination is obtained by studying the restriction fragment length polymorphism of the PCR products. The experience of three laboratories using this technique in the context of organ or bone marrow transplantation is reported.

Alleles↗

Choleretic activity of 3-[ring substituted benzotriazol-1(2)-yl]alkanoic and alkenoic acids.

In order to investigate the influence of structural modifications on the high choleretic activity of 3-(benzotriazol-1-yl)butanoic acid, a set of new benzotriazolyl alkanoic and alkenoic acids was prepared and, together with some other acids previously described, tested in rats by i.v. administration at the dose of 0.5 mmol/kg. Most of the tested compounds exhibited a good choleretic activity comparable with or higher than that of the model acid and of dehydrocholic acid (+56% mean increase of bile volume during 4 hours). Influence of nature and position of substituents was shown in some cases: a moderate decrease of activity was observed for methoxy derivatives and for the introduction of a methyl group in position 6, while a trifluoromethyl group in the same position enhanced the activity (10). Activity was maintained after the introduction of unsaturation in the chain (17,18), but was completely suppressed when unsaturation was associated with a shortening of the alkenoic chain (16). Moving the butanoic chain from position 1 to position 2 in the case of the nitroderivative (15) produced a striking increase of activity (from +42 to +118 mean variation of bile volume during 4 hours), while the same change in the unsubstituted acid 1 abolished the activity.

Animals↗

[Intermittent exotropia: evaluation of results on the basis of different treatments].

The aim of the study is to evaluate the results obtained in treatment of Intermittent Exotropia with the therapeutic programme applied at the Orthoptic Centre of Sassari Oculist Clinic. 250 patients were considered; 176 completed treatment. The patients were divided into four groups according to the kind of treatment adopted: orthoptic exercises, surgery (double recession of lateral rectus), exercises and surgery, no therapy. Results were evaluated by measuring the acquired state of orthophoria or residual exotropia: less than 10 prismatic diopters (excellent result); residual exotropia between 11 and 20 prismatic diopters (unsatisfactory result); residual exotropia > 20. The highest percentage of excellent results was found in those patients who underwent surgery but only among those who completed the therapy with cycles of orthoptic exercises. Conversely, the worst results were evident in patients who followed no therapeutic programme.

Adolescent↗

L-dopa stimulates c-fos expression in dopamine denervated striatum by combined activation of D-1 and D-2 receptors.

Administration of L-dopa to unilaterally 6-hydroxydopamine-lesioned rats, activates the early gene c-fos in the lesioned caudate-putamen. D-1 receptor blockade by SCH 23390, prevented L-dopa-induced Fos-like immunoreactivity in the whole caudate-putamen, while D-2 receptor blockade by raclopride reduced Fos-like immunoreactivity only in the dorso-lateral portion. The results suggest that L-dopa induces c-fos primarily through an activation of D-1 receptors, while D-2 receptor stimulation plays a facilitatory influence on D-1-mediated c-fos expression.

Animals↗

Acetyl-L-carnitine and Alzheimer's disease: pharmacological considerations beyond the cholinergic sphere.

Since ALCAR and L-carnitine are "shuttles" of long chain fatty acids between the cytosol and the mitochondria to undergo beta-oxidation, they play an essential role in energy production and in clearing toxic accumulations of fatty acids in the mitochondria. ALCAR has been considered of potential use in senile dementia of the Alzheimer type (SDAT) because of its ability to serve as a precursor for acetylcholine. However, pharmacological studies with ALCAR in animals have demonstrated its facility to maximize energy production and promote cellular membrane stability, particularly its ability to restore membranal changes that are age-related. Since recent investigations have implicated abnormal energy processing leading to cell death, and severity-dependent membrane disruption in the pathology of Alzheimer's disease, we speculate that the beneficial effects associated with ALCAR administration in Alzheimer patients are due not only to its cholinergic properties, but also to its ability to support physiological cellular functioning at the mitochondrial level. This hypothetical mechanism of action is discussed with respect to compelling supportive animal studies and recent observations of significant decrease of carnitine acetyltransferase (the catalyst of L-carnitine acylation to acetyl-L-carnitine) in autopsied Alzheimer brains.

Acetylcarnitine↗

Blockade of muscarinic receptors potentiates D1 dependent turning behavior and c-fos expression in 6-hydroxydopamine-lesioned rats but does not influence D2 mediated responses.

In rats with a unilateral 6-hydroxydopamine lesion of the dopaminergic nigrostriatal pathway, blockade of muscarinic receptors by scopolamine potentiates the contralateral turning induced by selective dopaminergic D1 agonists (SKF 38393, A 68930), but does not influence the contralateral turning induced by the D2 agonist LY 171555. Studies on the expression of the early gene c-fos as reflected by the immunohistochemical demonstration of the Fos protein, show that administration of scopolamine (5 mg/kg, i.p.) potentiates c-fos expression elicited by SKF 38393 (1.5 mg/kg, s.c.) in the caudate-putamen of the lesioned side. The results indicate that cholinergic transmission is differentially involved in the behavioral expression of D1 versus D2 receptor stimulation in a denervated condition and suggest that blockade of central cholinergic transmission might be useful in improving the antiparkinsonian efficacy of D1 receptor agonists.

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

Intravenous boluses and continuous infusions of L-dopa methyl ester in fluctuating patients with Parkinson's disease.

In six patients with Parkinson's disease exhibiting severe "on-off" phenomena, a 200-mg intravenous bolus of either L-DOPA or of its methyl ester were equally effective in reversing motor deficits, although the duration of action of the methyl ester was shorter. There were no marked differences in pharmacokinetic parameters for L-DOPA plasma levels after administration of L-DOPA and the methyl ester. In three patients, optimal infusion rates for the maintenance of mobility were established for L-DOPA and L-DOPA methyl ester. Both drugs were able to maintain patients "on" throughout a 12-h infusion period. However, on average the optimal infusion rate of L-DOPA methyl ester was 2.7 times greater than that for L-DOPA. There was no marked difference in the plasma levels of L-DOPA achieved, but 3-O-methyl DOPA levels increased more after infusion of L-DOPA methyl ester than after infusion of L-DOPA itself. The half-life of elimination and volume of distribution of L-DOPA formed from the methyl ester were markedly increased compared with values obtained after either an intravenous bolus of methyl ester or after an intravenous infusion of L-DOPA itself. An intravenous bolus of L-DOPA methyl ester produces an equivalent magnitude of clinical response to the same dose of L-DOPA. However, higher optimal infusion rates of methyl ester than L-DOPA are required to produce continuous effect. The pharmacokinetic handling of L-DOPA methyl ester given by intravenous infusion may differ from that of L-DOPA when given by the same route.

Aged↗

Clinical issues of cognitive enhancers in Alzheimer disease.

Cognitive enhancers is a provocative and vague label for drugs used to treat dementia of the Alzheimer type. Several issues have to be carefully considered in order to perform reliable clinical trials with such compounds. The lack of an animal model appropriately matching the human pathology, the difficulty in finding worldwide criteria for clinical diagnosis and determining which patients are eligible and how they are best tested, methods of treatment, and interpreting results are undoubtedly the major problems to be solved. A review of the literature points out that the "day-after" approach of treatment (once severe neuropathological damage has been established) is no longer feasible, or has limited advantages. A different pharmacological approach, based on preventive measures during the first stages of the neurodegeneration, seems mandatory.

Alzheimer Disease↗

The clinical efficacy of oral levodopa methyl ester solution in reversing afternoon "off" periods in Parkinson's disease.

We compared the efficacy of a single dose of an oral solution of levodopa methyl ester (ME) to that of standard levodopa, in the form of a single dose of Madopar, in reversing afternoon "off" periods in 12 patients with Parkinson's disease (PD). The highly soluble ME solution led to a significantly more rapid reversal of "off" periods. This preparation may therefore convey a clinical advantage in patients experiencing motor fluctuations whilst taking multiple daily dosages of levodopa, particularly in those with long or highly variable latency to the next "on" period.

Administration, Oral↗