Preventive care delivered within Public Dental Service after caries risk assessment of young adults.

OBJECTIVES: To study preventive care provided to young adults in relation to their estimated risk category over a 3-year period. METHODS: The amount and type of preventive treatment during 3 years was extracted from the digital dental records of 982 patients attending eight public dental clinics. The baseline caries risk assessment was carried out by the patient's regular team in four classes according to a predetermined model, and the team was responsible for all treatment decisions. Based on the variables 'oral health information', 'additional fluoride' and 'professional tooth cleaning', a cumulative score was constructed and dichotomized to 'basic prevention' and 'additional prevention'. RESULTS: More additional preventive care was provided to the patients in the 'low-risk' and 'some risk' categories than to those classified as 'high' or 'very high' risk (OR = 2.0, 95% CI 1.4-3.0; P < 0.05). Professional tooth cleaning and additional fluorides were most frequently employed in the 'low-risk' and 'some risk' categories, respectively. Around 15% of the patients in the high-risk categories did not receive additional preventive measures over the 3-year period. There was an insignificant tendency that patients with additional prevention developed less caries than those that received basic prevention in all risk categories except for the 'very high-risk' group. CONCLUSION: The caries risk assessment process was not accompanied by a corresponding targeted individual preventive care in a cohort of young adults attending public dental service. Further research is needed how to reach those with the greatest need of primary and secondary prevention.

Angular range for reflection of p-polarized light at the surface of an absorbing medium with reflectance below that at normal incidence.

The range of incidence angle, 0 < phi < phi(e), over which p-polarized light is reflected at interfaces between transparent and absorbing media with reflectance below that at normal incidence is determined. Contours of constant phi(e) in the complex plane of the relative dielectric constant epsilon are presented. A method for determining the real and imaginary parts of the complex refractive index, epsilon(1/2) = n + jk, which is based on measuring phi(e) and the pseudo-Brewster angle phi(pB), is viable in the domain of fractional optical constants, n, k < 1.

Scopolamine does not restore normal conditioned avoidance performance in raclopride-treated rats.

Several studies have shown antagonism by anticholinergics of antipsychotic-induced suppression of conditioned avoidance behavior, as well as of catalepsy, in rats. These observations provide pharmacological evidence for these behaviors mediated via nigro-striatal dopaminergic projections, as well as known dopaminergic-cholinergic interactions in the neostriatum. The objective of the present study was to examine the quality of behavioral change produced by scopolamine (0.25-1.00 mgkg(-1) s.c.) on conditioned avoidance behavior, by itself, and in combination with raclopride (0.1 mgkg(-1) s.c.) in the rat. Adult male Wistar rats were trained to perform a conditioned avoidance response requiring a brightness discrimination. A two-way avoidance shuttle-box was used with the modification that there were two passages in the partition separating the two compartments of the shuttle-box. In order to make a correct avoidance in the response to white noise conditioned stimulus, the rat had to take background light into consideration. Correct passage under dim background conditions was to the left and, with increased background lights, to the right. A weak, intermittent, electric shock (approximately 0.2 mA) was used as unconditioned stimulus. Scopolamine by itself (0.25-1.00 mgkg(-1) s.c.) disrupted the visual discrimination without affecting avoidance performance. As expected, raclopride (0.1 mgkg(-1) s.c.) produced a suppression of conditioned avoidance behavior. A dose of 1.00 mgkg(-1) of scopolamine was needed to restore raclopride-induced suppression of conditioned avoidance behavior. Thus, restoration of the avoidance behavior by scopolamine treatment was not possible at doses that allow normal performance of the visual discrimination. It is concluded that anticholinergics do not restore normal behavior after neuroleptic-induced suppression of conditioned avoidance behavior.

In vivo characterization of novel full and partial 2-(4-aminophenyl)-N,N-dipropylethylamine dopamine D(2) receptor agonists.

Behavioral and biochemical techniques were used to compare the in vivo intrinsic efficacy of two new 2-(4-aminophenyl)-N, N-dipropylethylamine dopamine D(2) receptor agonists, 2-(4-amino-3-trifluoromethylphenyl)-N-N-dipropyl-ethylamine (NBF-203) and 2-(4-amino-3-bromo-5-trifluoromethylphenyl)-N-N-dipropylethylamine (NBF-234). Adult male Sprague-Dawley rats were used as experimental animals. NBF-203 was characterized as a full dopamine D(2) receptor agonist, whereas NBF-234 displayed properties of a partial agonist, or antagonist, at dopamine D(2) receptors. Thus, NBF-203 produced effects similar to those of apomorphine in models for dopamine synthesis, release and turnover. As a strong indication of markedly less intrinsic efficacy, the administration of NBF-234 did not result in antagonism of reserpine-induced suppression of locomotor activity in the presence of (+/-)-1-phenyl-2,3,4,5, -tetrahydro-(1H)-3-benzazepine-7,8-diol HCl (SKF-38393)-induced dopamine D(1) receptor activation. The present series of compounds offer the possibility of adjusting intrinsic efficacy at dopamine D(2) receptors, and such fine-tuning could be an important strategy in the search for optimal antipsychotic or antiparkinson drugs within the partial dopamine D(2) receptor agonist concept.

Suggestive evidence for inhibitory effects of galanin on mesolimbic dopaminergic neurotransmission.

The objective was to examine effects of galaninrat on forebrain monoamine synthesis and on spontaneous locomotor activity in the rat. The rate of monoamine synthesis was estimated by measuring the accumulation of l-DOPA and 5-HTP, following inhibition of cerebral aromatic l-amino acid decarboxylase by means of NSD-1015 (100 mg kg-1 i.p.), after i.c.v. or intracerebral administration of galanin in adult male Wistar rats. Spontaneous locomotor activity was observed in an automated open-field arena ( approximately 0.5 m2). The i.c.v. administration of galanin (0.5-5.0 nmol bilaterally) produced a dose-dependent, statistically significant, increase in DOPA accumulation throughout the neostriatum, and in the olfactory bulb, indicating an increase in the rate of DA synthesis. No increase was observed in brain areas where noradrenaline is the predominant catecholamine, such as the neocortex or the ventral hippocampus. In addition, there was a tendency for an increase in 5-HTP accumulation in the dorso-lateral neostriatum and in the accumbens. The same i.c.v. administration of galanin produced a dose-dependent, and statistically significant, decrease in spontaneous locomotor activity. The effect on forebrain DA synthesis could also be produced by local bilateral application of galanin (2x1 nmol) into the ventral tegmental area, but not the nucleus accumbens (2x2 nmol). There were no effects on forebrain DOPA or 5-HTP accumulation by the local application of galanin into the locus coeruleus, or into the dorsal raphe nucleus. It is concluded that the neuropeptide galanin modulates forebrain dopaminergic neurotransmission. The effect appears to be mediated at the somato-dendritic level of the meso-neostriatal pathway, and could perhaps be utilized to normalize perturbations ascribed to dysfunction in this neuronal pathway, such as schizophrenia.

In vivo effects of remoxipride and aromatic ring metabolites in the rat.

The in vivo effects of remoxipride, in relation to some of its identified metabolites, were investigated in adult male Sprague-Dawley rats. The methods used included: (1) estimation of the in vivo rate of brain monoamine synthesis by measuring the accumulation of dihydroxyphenylalanine and 5-hydroxytryptophan after decarboxylase inhibition; (2) observations of spontaneous locomotor activity in a photocell-equipped open-field arena ( approximately 0. 5 m2); (3) treadmill locomotion ( approximately 4 m min-1); (4) inclined grid (60 degrees ) catalepsy test; (5) d-amphetamine-induced (1.0 mg kg-1) hyperlocomotion;(6) quinpirole-induced (0.4 mg kg-1) hypothermia. By use of one or more of these tests, the findings with remoxipride were as follows: First, remoxipride had a late onset of action (up to 3 h). Second, potency and efficacy depended on exposure to hepatic metabolism. Thus, intraperitoneal administration was more effective than the subcutaneous route, whereas virtually all biological effects were lost on intracerebroventricular administration. The ED50 values (micromol kg-1, neostriatal dihydroxyphenylalanine accumulation) for remoxipride and a range of its phenolic aromatic ring metabolites were: remoxipride (approximately 20), NCQ-344 (approximately 0.01), FLA-797 (approximately 0.1), FLA-908 (approximately 2.2), NCQ-436 (approximately 25) and NCQ-469 (approximately 30). Considering remoxipride as a nonclozapine atypical antipsychotic drug, together with the fact that remoxipride behaves as a prodrug in the laboratory studies above, further characterization of the pharmacodynamic profile of its metabolites remains a challenge.

Stimulation of brain dopamine autoreceptors by remoxipride administration in reserpine-treated male rats.

Male Sprague-Dawley rats were treated subcutaneously with reserpine (5 mg kg-1, -18 h) and with the aromatic amino acid decarboxylase inhibitor, NSD-1015 (3-hydroxybenzylhydrazine) (100 mg kg-1 -30 min). Remoxipride 0.8, 3.2 or 12.8 mg kg-1 was administered subcutaneously at -50 min. Immediately following decapitation (0 h), the ventral striatum and the anterior neocortex were dissected. Dopa and 5-hydroxytryptophan accumulation in these brain areas were analysed by HPLC with electrochemical detection. Reserpine produced a marked increase in striatal and neocortical dopa accumulation, in comparison with glucose vehicle + NSD-1015-treated controls, and this increase was dose-dependently antagonized by remoxipride treatment. Thus, together with demonstrated dopamine receptor antagonist actions in intact animals, remoxipride behaves as a mixed dopamine receptor agonist-antagonist. Such properties could contribute to the favourable endocrine and extrapyramidal side effect profile of remoxipride as an antipsychotic agent.

Specific effects by the psychotomimetic drugsd-amphetamine and phencyclidine on the performance of an aversely motivated successive visual discrimination in the rat.

Rats were trained to perform a conditioned avoidance response to white noise in a conventional two-compartment "shuttle-box". The partition between the compartments had two openings, however, and the correct passage (leftor right) was signalled by changes in background illumination. In this situation the psychotomimetic compoundsd-amphetamine (4 mg kg(-1) IP) and phencyclidine (PCP) (2 mg kg(-1) SC) were found to selectively disrupt the visual discrimination. Thed-amphetamine-induced abnormal behavior in this situation has previously been linked to excessive dopamine (DA) receptor stimulation, not controlled by nerve impulse flow and its regulation by important local feed-back mechanisms. Thus, the psychotomimetic effects produced by this compound should not only by due to increased DA receptor activationper se, but also to a disruption of normal patterns of firing and release in dopaminergic neurons. There is evidence to suggest that PCP via an excitatory amino acid (EAA) receptor produces a similar net effect on brain meso-limbic dopaminergic neurotransmission via an increased rate of firing, accompanied by regularization of firing (loss of burst activity). In support for a mediation of PCP-induced effects via EAA receptors, the local application of kynurenic acid into the ventral forebrain (4.7µg, bilaterally) was found also to produce a selective disruption of discriminative performance. It should be noted, however, thatd-amphetamine-induced loss of discriminative behavior, but not that induced by PCP, was antagonized by haloperidol (0.1-0.2 mg kg(-1) IP) administration. It is thus possible that at least some effects of PCP in this situation are mediated on the efferent side of the dopaminergic neuron. It is suggested that the abnormal behavior, as evidenced by a loss of discriminative (but not avoidance) behavior, is due to disruption of normal, feed-back regulated, nerve impulse flow.

Effects of a sustained release formulation of the gonadotrophin-releasing hormone agonist histrelin on serum concentrations of gonadotrophins and oestradiol, and ovarian LH/human chorionic gonadotrophin receptor content in the rat.

Pituitary and ovarian function were studied during the loss and recovery of oestrous cyclical activity in rats following treatment with a sustained release formulation of the gonadotrophin-releasing hormone (GnRH) agonist [imidazole benzyl-D-His6,Pro9-ethylamide]-GnRH (histrelin). A single s.c. injection of microencapsulated histrelin (10-300 micrograms peptide/kg) induced a dose-dependent disruption of normal oestrous cyclical activity with a persistent dioestrous-like vaginal cytology. In preliminary studies, pituitary gland stimulation and desensitization were demonstrated when serum LH and FSH levels were greater 1 week after administration of 10 micrograms microencapsulated histrelin/kg compared with 300 micrograms microencapsulated histrelin/kg. Changes in pituitary and ovarian function were assessed over time following injection of microencapsulated histrelin (100 micrograms peptide/kg). LH secretion was maximal within 8 h and then gradually declined, remaining at dioestrous levels from days 7 to 28. Serum oestradiol concentrations remained low and rose above dioestrous levels only on day 28. In contrast, ovarian LH/human chorionic gonadotrophin (LH/hCG) receptor content fell within 8 h and, after a nadir on day 7, slowly returned to dioestrous levels by day 28. The increase in ovarian LH/hCG receptor content preceded any significant change in pituitary gonadotrophin secretion, indicating a differential pattern of recovery for pituitary and ovarian function. Subsequent studies tested the possibility that these temporal differences in pituitary and ovarian function may result from histrelin acting directly on these tissues. Treatment with histrelin microcapsules (300 micrograms peptide/kg) prevented any increase in LH secretion in response to a GnRH challenge 3 days later, indicating a direct action of histrelin on the pituitary gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Photocell measurements of rat motor activity. A contribution to sensitivity and variation in behavioral observations.

A new, photocell-equipped, activity meter is described. The motor activity is observed in a large square, "open field", arena (approximately 0.5 m2) suited for activity observations of rats or other similarly sized animals. Horizontal and vertical activity is recorded at two levels (8 x 8 photocells at each level). Information from each photocell, individually fed into a microcomputer, was used to measure total motor activity, activity in the periphery of the arena, forward locomotion, rearing (total and peripheral), and speed of movement. The equipment has been evaluated by studying the effects of six psychoactive compounds, d-amphetamine, apomorphine, phencyclidine, raclopride, haloperidol, and 8-hydroxy-2-(di-n-propylamino) tetralin. In addition, a graph on the distribution of time intervals between successive photocell beam interruptions, and the within- and between-session habituation in normal animals is provided.

Behavioural and biochemical effects of subchronic treatment with raclopride in the rat: tolerance and brain monoamine receptor sensitivity.

Male Sprague-Dawley rats were treated with the dopamine (DA) D2 receptor blocking agent raclopride 0.5 or 8.0 mg kg-1 subcutaneously (1.0 and 16.0 mumol kg-1, respectively), twice daily for 21 days. The animals treated with raclopride gained weight at the same rate as saline controls, and gross observation did not indicate any behavioural abnormalities due to the subchronic raclopride treatment. Possible changes in brain DA receptor sensitivity due to prolonged blockade of DA receptors were evaluated in behavioural and biochemical models. There were no effects on locomotor activity, as observed by means of photobeam-equipped activity cages, 24 hr or 72 hr after withdrawal of 0.5 or 8.0 mg kg-1 subchronic raclopride treatment. Twenty-four hr after withdrawal of the raclopride treatment there was an increased post-synaptic DA receptor sensitivity as evidenced by increased behavioural and biochemical responses to apomorphine, and by an attenuated response to acute raclopride treatment, 0.1 mg kg-1. Thus, there was an increase in locomotor activity by the apomorphine treatment in animals pretreated with the 8 mg kg-1 dose, as compared to the response obtained in saline controls. Furthermore, the suppression of locomotor activity in saline controls produced by acute raclopride treatment was dose-dependently antagonized by the raclopride pretreatment and this also applied to the increase in striatal DOPAC levels produced by acute raclopride treatment. Finally, there was an increased DA receptor sensitivity presynaptically as evidenced by an enhanced effect on striatal DOPA levels by apomorphine in rats treated with NSD 1015 and reserpine.(ABSTRACT TRUNCATED AT 250 WORDS)

Loss of discriminative avoidance behavior by local application of kynurenic acid into the nucleus accumbens of the rat.

Male Sprague-Dawley rats, trained to perform a visual discrimination, were administered kynurenic acid, an antagonist of excitatory amino acid receptors, 4.7 micrograms bilaterally into the nucleus accumbens. The performance of the visual discrimination was impaired 15, but not 360, min after administration. In addition, motor activity in the test apparatus was markedly increased by the treatment, whereas no effects were noted when the animals were observed in an open field. The abnormal behavior produced by kynurenic acid has previously been observed after administration of high doses of compounds like d-amphetamine and L-DOPA, and generally discriminative behavior has been shown to be highly dependent on normal impulse mediated release of dopamine in brain. The present results show that this behavior also is dependent on an intact excitatory amino acid neurotransmission.

Suppression of conditioned avoidance behavior by the local application of (-)sulpiride into the ventral, but not the dorsal, striatum of the rat.

The local application of (-)sulpiride, 200 ng side-1, into the nucleus accumbens produced a suppression of conditioned avoidance behavior in male rats, 10 and 90 min after injection. The decrease in avoidance behavior was accompanied by a decrease in motor activity, as evidenced by changes in the number of intertrial crosses. When injected into the dorsolateral neostriatum, or the amygdala, (-)sulpiride produced a suppression of conditioned avoidance behavior at the 90-min time interval only. Considering diffusion from the injection site, as indicated by an increase in local dopamine turnover [(DO-PAC + HVA) DA-1], the effects obtained in the dorsolateral neostriatum, and possibly also the amygdala, 90 min after injection could be due to diffusion to the nucleus accumbens. The local application of (-)sulpiride into the posterior neostriatum, or into the prefrontal cortex, produced no statistically significant effect on conditioned avoidance behavior 10 or 90 min after injection. It is concluded that the performance of conditioned avoidance behavior in the rat is critically dependent on an intact dopaminergic neurotransmission in the nucleus accumbens or adjacent areas of the ventral striatum.

Phencyclidine-induced disruption of an aversely motivated two-choice successive discrimination in the rat.

Rats were trained to performed an aversely motivated discriminative task in a shuttle-box. The administration of phencyclidine (PCP), 2 mg kg-1 SC at -20 min, produced disruption of discriminative performance and an increase in intertrial crosses. There were no changes in avoidance performance or in avoidance latency. Pretreatment with haloperidol, 0.1 or 0.2 mg kg-1 SC at -40 min, or remoxipride 8 mg kg-1 IP at -30 min, did not antagonize the PCP-induced disruption of discriminative performance, nor was the PCP-induced increase in number of intertrial crosses antagonized. In fact, there appeared to be a further increase in intertrial crosses, above PCP levels, by haloperidol treatment and this effect was statistically significant after remoxipride treatment. The present results, together with previous observations that also d-amphetamine disrupts discriminative conditioned avoidance behavior, suggest the possibility that this model could be used in the search for new, non-dopaminergic, antipsychotic drugs.

Loss of dopamine uptake sites labeled with [3H]GBR-12935 in Alzheimer's disease.

The binding of the dopamine uptake inhibitor [3H]GBR-12935 to postmortem putamen from a control group and patients with Alzheimer's disease/senile dementia of Alzheimer type (AD/SDAT) or vascular dementia (VD) was studied. The binding density (Bmax) in AD/SDAT was significantly reduced to 50% of control. A reduction of Bmax in VD was also noted, but it did not reach statistical significance. No differences in apparent binding affinity (Kd) between controls and dementia groups were obtained. The concentrations of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT) and homovanillic acid were also determined. The concentrations of DA and DOPAC were reduced by 30-40% in AD/SDAT and VD, but the reductions did not reach statistical significance. The concentration of 3-MT was reduced by 40% in AD/SDAT and by 30% in VD. The [3H]GBR-12935-binding densities correlated significantly with corresponding concentrations of DA in control brains. It is suggested that the loss of [3H]GBR-12935-binding sites in human putamen in AD/SDAT reflects a degeneration of dopamine neurites.

Profile of an oxytocin antagonist, RWJ 22164 for treatment of preterm labor in laboratory models of uterine contractility.

An oxytocin antagonist, 1-deamino-[D-TYR(Oethyl)2,THR4,ORN8]oxytocin (RWJ 22164; dTVT), has recently been characterized in models of uterine contractility. Studies were undertaken to characterize the action of dTVT further on both oxytocin- and vasopressin-induced increases in uterine contractility both in vitro and in situ models and in a model of preterm labor. In these studies, dTVT was found to be a specific competitive inhibitor of both oxytocin- and vasopressin-induced contractions of both pregnant and nonpregnant guinea pig uterus in vitro. In situ, the intravenous administration of dTVT induced a dose-dependent inhibition of oxytocin- and vasopressin-induced contractions in a guinea pig model which measures uterine activity as changes in uterine perfusion pressure. Further studies demonstrated that the intravenous infusion of dTVT delays ongoing labor.

5-Hydroxytryptamine-sensitive [3H]imipramine binding of protein nature in the human brain. II. Effect of normal aging and dementia disorders.

Recently, a high-affinity [3H]imipramine binding site of protein nature that appeared related to the 5-hydroxytryptamine (5-HT, serotonin) uptake mechanism was demonstrated in the rat brain. In a preceding paper a similar [3H]imipramine binding site of protein nature and displaceable by 5-HT was demonstrated in the human brain. Most previous [3H]imipramine binding studies of the human brain have used desipramine-sensitive binding, which appears to contain a significant amount of additional binding not related to 5-HT neurons. Therefore this study of the human brain in the normal aging, in Alzheimer's disease/senile dementia of Alzheimer type (AD/SDAT) and in multiinfarction dementia (MID) presents data on 5-HT-sensitive [3H]imipramine binding. The influence of normal aging (17-100 years) was studied in the frontal and cingulate cortices, in the putamen, caudate nucleus, amygdala and in the hippocampus. An age-related change in 5-HT-sensitive [3H]imipramine binding was only noted in the cingulate cortex with a 50% loss in Bmax over the adult age range. In contrast, desipramine-sensitive [3H]imipramine binding studied in the frontal cortex and in the putamen showed marked increases in Bmax with age which correlated with increases in Kd. It is suggested that these increases are related to an increased binding to lipophilic membrane components not related to 5-HT neurons. The 5-HT-sensitive [3H]imipramine binding (Bmax) was reduced to 60% of control in the cingulate cortex and to 50% in the putamen in AD/SDAT. In MID there was a 50% loss of [3H]imipramine binding sites (Bmax) in the putamen, but a 30% loss in the cingulate cortex did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of 1-deamino-[D-Tyr(Oethyl)2, Thr4, Orn8] vasotocin, an oxytocin antagonist, in animal models of uterine contractility and preterm labor: a new tocolytic agent.

We attempted to characterize the ability of a new oxytocin derivative, 1-deamino[D-Tyr(Oethyl)2,Thr4,Orn8] vasotocin (ORF 22164), to antagonize the action of oxytocin in several in vitro and in vivo animal models of uterine hyperactivity. In these studies, the derivative was found to be a specific competitive inhibitor of oxytocin-induced contractions of pregnant guinea pig uterus in vitro. In addition, its intravenous administration induced a dose-dependent inhibition of oxytocin-induced uterine contractions in situ. Finally, like ritodrine, the drug induced a dose-dependent delay of ongoing labor in rats. These results suggest that 1-deamino-[D-Tyr(Oethyl)2,Thr4,Orn8] vasotocin, unlike ritodrine, is a potent and specific antagonist of oxytocin-induced uterine contractions and thus may have potential clinical utility in the treatment of preterm labor.

Evaluation of drugs for arrest of premature labor in a new animal model.

Reported are pharmacologic data from a new animal model used for evaluating drugs from several therapeutic classes for their potential use in the treatment of premature labor. This model measures the spontaneous delivery time between the first and second rat pups in a term pregnancy. In control animals, this averaged 16.3 +/- 4.2 minutes. Ethanol (3.5 gm/kg) and the beta-agonists ritodrine (12.5 mg/kg) and albuterol (0.25 mg/kg) significantly delayed delivery of the second pup. The calcium blockers nifedipine, verapamil, and diltiazem were the most active of all compounds tested in this model. The nonsteroidal anti-inflammatory agents indomethacin and naproxen were inactive at doses as high as 5 and 25 mg/kg, respectively. Metiamide, an H2-antagonist, and dimenhydrinate, an H1-antagonist, were inactive.

Corneal endothelial cell measurements in megalocornea.

A pedigree of megalocornea manifested many of the characteristic features as well as some less common features of the disorder. Endothelial specular microscopy of affected patients disclosed normal endothelial cell densities and morphologic characteristics and increased total endothelial cell populations, suggesting a process of total corneal hyperplasia. In contrast, unpublished data indicate diminished densities in congenital glaucoma, a finding more consistent with corneal distention. We conclude that specular microscopy may be of value in differentiating the two disorders, although larger series are necessary for confirmation.