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Biomedical subjects

G Shapiro

Publications and source records attributed to G Shapiro.

At least 55 records · Page 3Linked to original sources
PubMed1993

SDZ ENS 163 a novel pilocarpine like drug: pharmacological in vitro and in vivo profile.

The thiolactone analogue of pilocarpine, SDZ ENS 163, acts in vitro and in vivo as a partial agonist at M1/M3 and as an antagonist at M2 muscarinic receptors. In vitro, the properties of SDZ ENS 163 have been investigated in several functional models for muscarinic receptors: it is a full agonist at M1 (rat superior cervical ganglion, carbachol = 100%) and a partial agonist at M3 receptors (guinea pig ileum). However, the drug shows antagonistic properties at M2 receptors (rat atria). Radioligand binding studies with 3H-N-methylscopolamine (3H-NMS) using CHO cells expressing m1 or m3 receptors indicate that SDZ ENS 163 does not discriminate between m1 and m3 receptors (Ki 1.5 and 2.4 microM respectively). Regarding phosphoinositide (PI) turnover in A9L cells, SDZ ENS 163 is a partial agonist at m1 receptors. In ex vivo neurochemical studies in rats SDZ ENS 163 displays effects characteristic of muscarinic antagonists regarding the turnover of ACh which is increased in the brain. At a similar dose-range SDZ ENS 163 accelerates PI metabolism in the rat brain in vivo and increases the energy of the low frequency band (2-5 Hz) in the rat hippocampal EEG. These effects observed in vivo are consistent with postsynaptic M1 agonistic and presynaptic M2 antagonistic activities. Since SDZ ENS 163 at centrally active doses exerts no peripheral cholinergic effects, it may be useful for the symptomatic treatment of Alzheimer's disease.

Acetylcholine↗
PubMed1993

Resorption of sintered synthetic hydroxyapatite by osteoclasts in vitro.

Primary rat bone marrow cells were cultured for periods of 8 d on hydroxyapatite discs produced by sintering compressed powder at 1130 degrees C. The disc surfaces were roughened using silicon carbide paper to create three groups of samples (n = 10) of differing surface topography. The culture conditions permitted both the differentiation and fusion of cells of the osteoclast lineage. Following culture, the cells were stained in situ for tartrate-resistant acid phosphatase activity, and the samples were prepared for scanning electron microscopy. Evidence of cellular resorption of the hydroxyapatite discs was seen on all samples. Small tartrate-resistant acid phosphatase positive cells created resorption pits of 15-25 microns diameter in the ceramic surface, which were morphologically similar to those found in natural bone tissue, while multinucleate cells caused erosion of the ceramic surface without pit formation. Statistical analyses showed that the total numbers of cells, tartrate-resistant acid phosphatase positive cells, and multinucleated cells were all higher on the roughened surfaces, although the resorption pits were more easily visualized on the smooth surfaces. The results clearly demonstrate that not only are osteoclasts capable of resorbing sintered hydroxyapatite but that the rugosity of the hydroxyapatite influences the fusion of osteoclast mononuclear precursors.

Animals↗
PubMed1992

SDZ ENS 163, a selective muscarinic M1 receptor agonist, facilitates the induction of long-term potentiation in rat hippocampal slices.

The effect of SDZ ENS 163; (+)-(3S,cis)-3-ethyldihydro-4-[(1-methyl-1H-imidazol-5-yl)methyl-2 (3H)- thiphenonedihydrogenphosphate], a selective muscarinic M1 agonist, on long-term potentiation (LTP) was studied in a rat hippocampal slice preparation. LTP was induced by theta-burst stimulation (TBS) delivered to the Schaffer/commissural fibers. In untreated slices delivery of 8 or 10 trains at 100 Hz induced a 27 +/- 8.3 and 54 +/- 7.2% potentiation of the amplitude of the excitatory postsynaptic potential (epsp), respectively (calculated as percentage of the pre-LTP amplitude). In slices pretreated with SDZ ENS 163 (2 x 10(-6) M, -30 min) delivery of 8 or 10 trains at 100 Hz induced a 62 +/- 8.4 and 54 +/- 7.1% potentiation of the epsp amplitude, respectively. In addition, treatment with SDZ ENS 163 (2 x 10(-6) M) increased the N-methyl-D-aspartate receptor-induced component of the epsp response to TBS from 21 +/- 3 (control) to 33 +/- 2%. Pretreatment with the muscarinic antagonist, scopolamine (6 x 10(-8) M), or with the M1 selective muscarinic receptor antagonist, pirenzepine (6 x 10(-8) M), did not affect LTP in untreated slices but inhibited the enhancement of LTP by SDZ ENS 163 (2 x 10(-6) M) completely. AF-DX 116 (10(-6) M, -60 min), a selective muscarinic M2 receptor antagonist did not affect LTP in control slices nor in slices treated with SDZ ENS 163 (2 x 10(-6) M). These data suggest that activation of muscarinic M1 receptors by SDZ ENS 163 facilitates the induction of LTP.

Animals↗
PubMed1992

SDZ ENS 163 is a selective M1 agonist and induces release of acetylcholine.

In the present study some pharmacological properties of the new muscarinic agonist SDZ ENS 163; (+)-(3S,cis)-3-ethyldihydro-4-[(1-methyl-1H-imidazol-5-yl) methyl-2(3H)-thiophenonedihydrogenphosphate] have been investigated. In the rat superior cervical ganglion, a model for M1 muscarinic receptors, SDZ ENS 163 induced concentration-dependent depolarizations (pD2 = 6.5 +/- 0.3; efficacy = 128 +/- 4.2% compared to carbachol). SDZ ENS 163 was a very weak partial agonist with respect to M2 receptor-induced decrease in contractile force in rat left atria (efficacy = 14 +/- 2.9%). In addition, SDZ ENS 163 competitively antagonized the effect of carbachol in rat left atria (pA2 = 5.8 +/- 0.2). In the guinea-pig ileum SDZ ENS 163 was a partial agonist with respect to force of contraction mediated by M3 receptors (pD2 = 5.3 +/- 0.1; efficacy = 72 +/- 4.2%). The oxotremorine-induced inhibition of the electrically stimulated release of acetylcholine (ACh) in rat hippocampal slices was reversed by SDZ ENS 163 (pA2 = 5.5 +/- 0.1). In addition after oral administration SDZ ENS 163 (3-10 mumol/kg) reduced brain ACh levels, which is indicative of increased ACh turnover. Finally, increases in energy of the low frequency band (2-5 Hz) were observed in rat hippocampal EEG after intraperitoneal administration of SDZ ENS 163 (0.3-30 mumol/kg). We conclude that SDZ ENS 163 is a selective M1 agonist in vitro with an additional M2 antagonistic effect. The in vivo effects of SDZ ENS 163 may result both from postsynaptic M1 agonistic as well as M2 receptor antagonistic activity. The unique pharmacological profile of SDZ ENS 163 may prove clinically favourable for treatment of cognitive deficits.

Acetylcholine↗
PubMed1992

Muscarinic activity of the thiolactone, lactam, lactol, and thiolactol analogues of pilocarpine and a hypothetical model for the binding of agonists to the m1 receptor.

Pilocarpine isosteres have been synthesized and characterized with regard to their in vitro muscarinic properties. The results indicate that the carbonyl oxygen of the lactone function of pilocarpine is of primary importance for agonist activity with the ether oxygen being of lesser or secondary importance. An X-ray structure determination for the hydrogen O,O'-ditoluoyltartrate salt of thiolactone pilocarpine isostere 2a has been performed. This compound has an unusual pharmacological profile exhibiting M1-agonist selectivity as well ass presynaptic antagonism. As a result this compound is also viewed as having therapeutic potential for Alzheimer's disease. A model for the binding of pilocarpine and other muscarinic agonists to the third transmembrane helix of the human m1 muscarinic receptor has been developed.

Animals↗
PubMed1991

Sound-based language play in four language-impaired subjects.

The production of sound-based language play in four language-impaired subjects was investigated. A battery of metalinguistic tests, incorporating the production of poems, nursery rhymes, alliteration and rhyme, was designed to assess the subjects' sound-based language play. The subjects' performance on these tests was compared with their performance on a battery of standardised language tests. Results indicated that the language-impaired subjects did not successfully involve themselves in sound-based language play. Furthermore, a decrease in sound-based language play was observed with an increase in the extent of the language impairment. Hence, a positive correlation was found between poor language competence and deficient metalinguistic skills. Diagnostic, therapeutic and theoretical implications are discussed.

Child↗
PubMed1991

Once daily triamcinolone acetonide nasal spray is effective for the treatment of perennial allergic rhinitis.

A randomized, double-blind, placebo-controlled, parallel group study was conducted in 11 centers to evaluate the safety and efficacy of a once-a-day regimen of 110 micrograms, 220 micrograms; and 440 micrograms of triamcinolone acetonide intranasal aerosol versus placebo in relieving the symptoms of rhinitis in 305 adult and older pediatric patients with perennial allergic rhinitis. Nasal stuffiness, nasal discharge, sneezing, nasal itching and the nasal index (the sum of the mean scores of the first three symptoms) averaged over the first 6 weeks and second 6 weeks of the study were significantly reduced in patients who received the 220 micrograms/day and the 440 micrograms/day dosages. The 110 micrograms/day group had a reduction in these nasal symptoms, but only the sneezing and nasal index were significantly (P less than .05) better than placebo. During the last 6 weeks of the study, patients were allowed to take oral back-up medication for their nasal symptoms; all three groups receiving triamcinolone nasal aerosol took less back-up medication than did the placebo group. There were no significant adverse effects or laboratory abnormalities noted during this study. Intranasal triamcinolone acetonide 220 micrograms and 440 micrograms, used once-a-day for 12 weeks is clinically and statistically superior to placebo for the treatment of perennial allergic rhinitis.

Administration, Intranasal↗
PubMed1990

A quantitative assessment of respiratory patterns and their effects on dentofacial development.

The purpose of this study was to assess the effects of quantitatively determined breathing patterns on dentofacial development in growing children. Forty-nine subjects ranging in age from 10 to 16 years participated in the breathing pattern assessment portion of this project. Oral, nasal, and total airflow were measured at separate times by means of a head-out body plethysmograph technique and the values were compared with the subjects' and parents' subjective perceptions of their breathing modes. These breathing pattern measurements also were compared to nasal airway resistance and nasal power. Temporal variation and cyclic respiration, which may play important roles in quantitative evaluations of childrens' breathing patterns, also were addressed. In addition, objective assessments of possible associations between dentofacial structure and respiration were made on 45 of these children. Most subjects' exhibited was either an oronasal or a completely nasal respiratory pattern. However, significant variation in breathing measures was evident among a number of subjects whose breathing was measured twice on the same day and on different days. No significant correlations were found between objectively measured and subjectively determined impressions of respiratory patterns. In addition, there was no association between nasal airway resistance or nasal power and plethysmograph recordings of percent of mouth breathing. Comparisons of measured breathing modes and dentofacial characteristics revealed a weak tendency among mouth breathers toward a Class II skeletal pattern and retroclination of maxillary and mandibular incisors. In contrast, subjective perception of mouth breathing was associated with increased anterior facial height and greater mandibular plane angles. Nasal power and resistance were not correlated with either dental or skeletal variables. This study presents evidence that determination of respiratory pattern is a complex issue for which methods must be refined and performed longitudinally.

Adolescent↗
PubMed1989

Communicative competence in a group of visually impaired children.

Aspects of verbal and non-verbal communicative competence of five visually-impaired six and seven year old children were investigated. The Profile of Communicative Appropriateness (Penn, 1983) was used to assess communicative competence in one discourse interaction with a known interlocutor (mother). The results indicated that the subjects were predominantly appropriate in terms of verbal communication, and predominantly inappropriate in terms of non-verbal communication. Severity of visual impairment influenced performance in terms of non-verbal communication. Research and therapeutic implications are discussed.

Blindness↗