Rumen volatile fatty acid molar proportions, rumen epithelial gene expression, and blood metabolite concentration responses to ruminally degradable starch and fiber supplies.

The objective of this work was to characterize rumen volatile fatty acid (VFA) concentrations, rumen epithelial gene expression, and blood metabolite responses to diets with different starch and fiber sources. Six ruminally cannulated yearling Holstein heifers (body weight = 330 ± 11.3 kg) were arranged in a partially replicated Latin square experiment with 4 treatments consisting of different starch [barley (BAR) or corn (CRN)] and fiber [timothy hay (TH) or beet pulp (BP)] sources. Treatments were arranged as a 2 × 2 factorial. Beet pulp and TH were used to create relative changes in apparent ruminal fiber disappearance, whereas CRN and BAR were used to create relative changes in apparent ruminal starch disappearance. Each period consisted of 3 d of diet adaptation and 15 d of dietary treatment. In situ disappearance of fiber and starch were estimated from bags incubated in the rumen from d 10 to 14. From d 15 to 17, rumen fluid was collected every hour from 0500 to 2300 h. Rumen fluid samples were pooled by animal/period and analyzed for pH and VFA concentrations. On d 18, 60 to 80 papillae were biopsied from the epithelium and preserved for gene expression analysis. On d 18, one blood sample per heifer was collected from the coccygeal vessel. In situ ruminal starch disappearance rate (7.30 to 8.72%/h for BAR vs. 7.61 to 10.5%/h for CRN) and the extent of fiber disappearance (22.2 to 33.4% of DM for TH vs. 34.4 to 38.7% of DM for BP) were affected by starch and fiber source, respectively. Analysis of VFA molar proportions showed a shift from propionate to acetate, and valerate to isovalerate on TH diets compared with BP. Corn diets favored propionate over butyrate in comparison to BAR diets. Corn diets also had higher molar proportions of valerate. Expression of 1 gene (SLC9A3) were increased in BP diets and 2 genes (BDH1 and SLC16A4) tended to be increased in TH diets. Plasma acetate demonstrated a tendency for a starch by fiber interaction with BAR-BP diets having the highest plasma acetate, but other metabolites measured were not significant. These results suggest that TH has the greatest effect on shifts in VFA molar proportions and epithelial transporters, but does not demonstrate shifts in blood metabolite concentrations.

Microbial dynamics and properties of aerobic granules developed in a laboratory-scale sequencing batch reactor with an intermediate filamentous bulking stage.

Aerobic granules offer enhanced biological nutrient removal and are compact and dense structures resulting in efficient settling properties. Granule instability, however, is still a challenge as understanding of the drivers of instability is poorly understood. In this study, transient instability of aerobic granules, associated with filamentous outgrowth, was observed in laboratory-scale sequencing batch reactors (SBRs). The transient phase was followed by the formation of stable granules. Loosely bound, dispersed, and pinpoint seed flocs gradually turned into granular flocs within 60 days of SBR operation. In stage 1, the granular flocs were compact in structure and typically 0.2 mm in diameter, with excellent settling properties. Filaments appeared and dominated by stage 2, resulting in poor settleability. By stage 3, the SBRs were selected for larger granules and better settling structures, which included filaments that became enmeshed within the granule, eventually forming structures 2-5 mm in diameter. Corresponding changes in sludge volume index were observed that reflected changes in settleability. The protein-to-polysaccharide ratio in the extracted extracellular polymeric substance (EPS) from stage 1 and stage 3 granules was higher (2.8 and 5.7, respectively), as compared to stage 2 filamentous bulking (1.5). Confocal laser scanning microscopic (CLSM) imaging of the biomass samples, coupled with molecule-specific fluorescent staining, confirmed that protein was predominant in stage 1 and stage 3 granules. During stage 2 bulking, there was a decrease in live cells; dead cells predominated. Denaturing gradient gel electrophoresis (DGGE) fingerprint results indicated a shift in bacterial community composition during granulation, which was confirmed by 16S rRNA gene sequencing. In particular, Janthinobacterium (known denitrifier and producer of antimicrobial pigment) and Auxenochlorella protothecoides (mixotrophic green algae) were predominant during stage 2 bulking. The chitinolytic activity of Chitinophaga is likely antagonistic towards Auxenochlorella and may have contributed to stage 3 stable granule formation. Rhodanobacter, known to support complete denitrification, were predominant in stage 1 and stage 3 granules. The relative abundance of Rhodanobacter coincided with high protein concentrations in EPS, suggesting a role in microbial aggregation and granule formation.

Degradable borate glass polyalkenoate cements.

Glass polyalkenoate cements (GPCs) containing aluminum-free borate glasses having the general composition Ag2O-Na2O-CaO-SrO-ZnO-TiO2-B2O3 were evaluated in this work. An initial screening study of sixteen compositions was used to identify regions of glass formation and cement compositions with promising rheological properties. The results of the screening study were used to develop four model borate glass compositions for further study. A second round of rheological experiments was used to identify a preferred GPC formulation for each model glass composition. The model borate glasses containing higher levels of TiO2 (7.5 mol %) tended to have longer working times and shorter setting times. Dissolution behavior of the four model GPC formulations was evaluated by measuring ion release profiles as a function of time. All four GPC formulations showed evidence of incongruent dissolution behavior when considering the relative release profiles of sodium and boron, although the exact dissolution profile of the glass was presumably obscured by the polymeric cement matrix. Compression testing was undertaken to evaluate cement strength over time during immersion in water. The cements containing the borate glass with 7.5 mol % TiO2 had the highest initial compressive strength, ranging between 20 and 30 MPa. No beneficial aging effect was observed-instead, the strength of all four model GPC formulations was found to degrade with time.

Fit for Purpose? The Suitability of Oral Health Outcome Measures to Inform Policy.

KNOWLEDGE TRANSFER STATEMENT: Oral health research and program evaluation should consider alternative outcome measures for population oral health other than the DMFT index.

Comparison of a SiO2-CaO-ZnO-SrO glass polyalkenoate cement to commercial dental materials: ion release, biocompatibility and antibacterial properties.

Ion Release and biocompatibility of a CaO-SrO-ZnO-SiO2 (BT 101) based glass polyalkenoate cement (GPC) was compared against commercial GPCs, Fuji IX and Ketac Molar. The radiopacity (R) was similar for each material, 2.0-2.8. Ion release was evaluated on each material over 1, 7, 30 and 90 days. BT 101 release included Ca (23 mg/L), Sr (23 mg/L) Zn (13 mg/L), Si (203 mg/L). Fuji IX release includes Ca (0.7 mg/L), Al (3 mg/L) Si (26 mg/L), Na (60 mg/L) and P (0.5 mg/L) while Ketac Molar release includes Ca (1 mg/L), Al (0.6 mg/L) Si (23 mg/L), Na (76 mg/L) and P (0.7 mg/L). Simulated body fluid trials revealed CaP surface precipitation on BT 101. No evidence of precipitation was found on Fuji IX or Ketac Molar. Cytotoxicity testing found similar cell viability values for each material (~60 %, P = 1.000). Antibacterial testing determined a reduced CFU count with BT 101 (2.5 × 10³) when compared to the control bacteria (2.4 × 104), Fuji IX (1.5 × 104) and Ketac Molar (1.2 × 104).

Cost-effectiveness analysis of silver diamine fluoride to divert dental general anaesthesia compared to standard care.

BACKGROUND: The aim is to perform a model-based cost-effectiveness analysis of a silver diamine fluoride (SDF) protocol intervention to divert dental general anaesthesia (DGA) among Victorian children aged 2-10 years. METHODS: Data inputs were based on an Australian single-cohort 2017/18 study. Intervention costs for standard care were derived from two subgroups of children: (1) children who received standard care without DGA, and (2) children who received standard care with DGA. Two scenarios were modelled due to limited post-follow-up data: (1) children receiving SDF had standard care without DGA (base-case scenario), and (2) children receiving SDF did not receive standard care without DGA (alternative scenario). A simple decision-tree model with probabilistic sensitivity analysis (PSA) estimated the incremental costs per diverted DGA. RESULTS: The probability of children requiring specialist referral and offered SDF, but the primary carer opted for DGA is 0.124 (SD 0.034), and the probability of children requiring DGA in standard care is 0.346 (SD 0.036). For both the base-case and alternative scenario, the incremental cost-effectiveness ratio outcome is dominant and their cost-effectiveness being either 74.8% or 100% respectively. CONCLUSIONS: The SDF protocol intervention is cost-effective dental caries management option for young children where referral for DGA is considered. © 2022 Australian Dental Association.

Cell wall stress depolarizes cell growth via hyperactivation of RHO1.

Cells sense and physiologically respond to environmental stress via signaling pathways. Saccharomyces cerevisiae cells respond to cell wall stress by transiently depolarizing the actin cytoskeleton. We report that cell wall stress also induces a transient depolarized distribution of the cell wall biosynthetic enzyme glucan synthase FKS1 and its regulatory subunit RHO1, possibly as a mechanism to repair general cell wall damage. The redistribution of FKS1 is dependent on the actin cytoskeleton. Depolarization of the actin cytoskeleton and FKS1 is mediated by the plasma membrane protein WSC1, the RHO1 GTPase switch, PKC1, and a yet-to-be defined PKC1 effector branch. WSC1 behaves like a signal transducer or a stress-specific actin landmark that both controls and responds to the actin cytoskeleton, similar to the bidirectional signaling between integrin receptors and the actin cytoskeleton in mammalian cells. The PKC1-activated mitogen-activated protein kinase cascade is not required for depolarization, but rather for repolarization of the actin cytoskeleton and FKS1. Thus, activated RHO1 can mediate both polarized and depolarized cell growth via the same effector, PKC1, suggesting that RHO1 may function as a rheostat rather than as a simple on-off switch.

The psychosocial impact of oral conditions during transition to secondary education.

AIM: Transition to secondary education is a significant life event. Little is known about the impact of oro-facial conditions during this time and how concerns may contribute as a risk factor to negative adaptation. The aim of the study was to explore experiences of young people with oro-facial conditions as they undergo the transition to secondary education. STUDY DESIGN: Qualitative interview and diary study. METHODS: Participants were children aged 11-12 years with a range of clinical conditions who attended a dental hospital. Participants completed a two-week diary during the transition and were interviewed about the diary and their experiences. The interviews were audio-taped and transcribed verbatim. RESULTS: Seventeen participants returned the diary and were interviewed; they described both changes in school environment and social interactions. A key finding was the concerns about aspects of themselves that children developed during this time. For some young people these concerns were about their oro-facial condition. No links between gender, severity of condition and experiences of school were apparent. CONCLUSION: Transition to secondary education affected young people to varying degrees. Timely treatment for those concerned about the condition of their teeth may improve the likelihood of positive adaptation.

The evolution and phylodynamics of serotype A and SAT2 foot-and-mouth disease viruses in endemic regions of Africa.

Foot-and-mouth disease (FMD) is a major livestock disease with direct clinical impacts as well as indirect trade implications. Control through vaccination and stamping-out has successfully reduced or eradicated the disease from Europe and large parts of South America. However, sub-Saharan Africa remains endemically affected with 5/7 serotypes currently known to be circulating across the continent. This has significant implications both locally for livestock production and poverty reduction but also globally as it represents a major reservoir of viruses, which could spark new epidemics in disease free countries or vaccination zones. This paper describes the phylodynamics of serotypes A and SAT2 in Africa including recent isolates from Cameroon in Central Africa. We estimated the most recent common ancestor for serotype A was an East African virus from the 1930s (median 1937; HPD 1922-1950) compared to SAT2 which has a much older common ancestor from the early 1700s (median 1709; HPD 1502-1814). Detailed analysis of the different clades shows clearly that different clades are evolving and diffusing across the landscape at different rates with both serotypes having a particularly recent clade that is evolving and spreading more rapidly than other clades within their serotype. However, the lack of detailed sequence data available for Africa seriously limits our understanding of FMD epidemiology across the continent. A comprehensive view of the evolutionary history and dynamics of FMD viruses is essential to understand many basic epidemiological aspects of FMD in Africa such as the scale of persistence and the role of wildlife and thus the opportunities and scale at which vaccination and other controls could be applied. Finally we ask endemic countries to join the OIE/FAO supported regional networks and take advantage of new cheap technologies being rolled out to collect isolates and submit them to the World Reference Laboratory.

Incorporation of novel 1-alkylcarbonyloxymethyl prodrugs of 5-fluorouracil into poly(lactide-co-glycolide) nanoparticles.

Incorporation of 1-alkylcarbonyloxymethyl prodrugs of 5FU into poly(lactide-co-glycolide) nanoparticles using nanoprecipitation methods gave increased loading efficiencies over that obtained using the parent drug substance. SEM studies revealed spherical nanoparticles of around 200nm in diameter, corresponding well with measurements made using photon correlation spectroscopy. The C(7) prodrug gave the best mean loading of 47.23%, which compared favourably to 3.68% loading achieved with 5FU. Loading efficiency was seen to follow the hydrophilic-lipophilic balance in the homologue series, where increases in lipophilicities alone were not good predictors of loading. Drug release, in terms of resultant 5FU concentration, was monitored using a flow-through dissolution apparatus. Cumulative drug release from nanoparticles loaded with the C(5) prodrug was linear over 6h, with approximately 14% of the total available 5FU dose released and with no evidence of a burst effect. The flux profile of the C(5)-loaded nanoparticles showed an initial peak in flux in the first sampling interval, but became linear for the remainder of the release phase. C(7)-loaded nanoparticles released considerably less (4% in 6h) with a similar flux pattern to that seen with the C(5) prodrug. The C(9)-loaded nanoparticles released less than 1% of the available 5FU over 6h, with a similar zero-order profile. The C(7) prodrug was deemed to be the prodrug of choice, achieving the highest loadings and releasing 5FU, following hydrolysis, in a zero-order fashion over a period of at least 6h. Given the lack of burst effect and steady-state flux conditions, this nanoparticulate formulation offers a better dosing strategy for sustained intravenous use when compared to that arising from nanoparticles made by direct incorporation of 5FU.

The incidence of adverse reactions following 4% septocaine (articaine) in children.

PURPOSE: The purpose of this study was to report the incidence of adverse events following the use of 4% Septocaine in children. METHODS: A prospective study was carried out on children attending university-based pediatric dental clinics for restorative core under local anesthesia. Data collection included patient demographics, medical history, amount and site of injection, and treatment complexity. Follow-up telephone interviews were conducted with the parents at 3, 5, 24, and 48 hours regarding prolonged paresthesia, soft tissue injury, and pain. RESULTS: Two hundred sixty-four 2 to 14 year-olds were recruited for the study. Complete interview information was obtained from 204 patients. Prolonged paresthesia at 3 hours postinjection was reported for 40% of the population and at 5 hours for 11%. Soft tissue injury occurred in 14% of the patients at 3 hours and was found to be highest among children younger than 7 years old. The lip was the most commonly affected site for accidental injury and it was not related to injection site. Twenty percent reported postprocedural pain at 3 and 5 hours post-treatment. CONCLUSIONS: Since prolonged numbness appears to be the most frequent adverse event and occurred primarily in children younger than 7 years old, parents need to be informed and reassured accordingly.

Synthesis, characterization, and in vitro cytocompatibility of Ga-bioactive glass/polymer hydrogel composites.

A bioactive glass series (0.42SiO2-0.10Na2O-0.08CaO-(0.40-x)ZnO-(x)Ga2O3) was incorporated in carboxymethyl cellulose-dextran hydrogels at three different loadings (0.05, 0.10, and 0.25 m2), and the resulting composites were characterized using scanning electron microscopy, physical swelling characteristics, and inductively coupled plasma optical emission spectroscopy. In vitro cytocompatibility was also evaluated for composite extracts in contact with L-929 mouse fibroblasts and MC3T3-E1 human osteoblasts. Scanning electron microscopy confirmed that glass particles were distributed throughout the hydrogels, and swelling studies showed that glass presence can increase the amount of fluid that can be absorbed by the hydrogels after seven days of immersion in phosphate-buffered saline by up to 180%. Several trends were observed in the inductively coupled plasma optical emission spectroscopy data, with the most important being the release of Ga3+ from both Ga-containing glasses at all three loadings, with a maximum of 4.7 mg/L released after 30 days of incubation in phosphate-buffered saline. Cell viability analysis suggested that most composite extracts did not decrease neither fibroblast nor osteoblast viability. These results indicate that it is possible to embed bioactive glass particles into carboxymethyl cellulose-dextran hydrogels, and upon submersion in aqueous media, release ions from the glass particles that may elicit therapeutic effects.

Structural characterization and anti-cancerous potential of gallium bioactive glass/hydrogel composites.

A bioactive glass series (0.42SiO2-0.10Na2O-0.08CaO-(0.40-X)ZnO-(X)Ga2O3) was incorporated into carboxymethyl cellulose (CMC)/dextran (Dex) hydrogels in three different amounts (0.05, 0.10, and 0.25m(2)), and the resulting composites were characterized using transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and (13)C Cross Polarization Magic Angle Spinning Nuclear Magnetic Resonance (CP MAS-NMR). Composite extracts were also evaluated in vitro against MG-63 osteosarcoma cells. TEM confirmed glass distribution throughout the composites, although some particle agglomeration was observed. DSC revealed that glass composition and content did have small effects on both Tg and Tm. MAS-NMR revealed that both CMC and Dex were successfully functionalized, that cross-linking occurred, and that glass addition did slightly alter bonding environments. Cell viability analysis suggested that extracts of the glass and composites with the largest Ga-content significantly decreased MG-63 osteosarcoma viability after 30days. This study successfully characterized this composite series, and demonstrated their potential for anti-cancerous applications.

Exploring child dental service use among migrant families in metropolitan Melbourne, Australia.

BACKGROUND: This study describes and explores factors related to dental service use among migrant children. METHODS: A cross-sectional analysis of baseline data from Teeth Tales, an exploratory trial implementing a community based child oral health promotion intervention. The sample size and target population was 600 families with 1-4 year old children from Iraqi, Lebanese and Pakistani backgrounds residing in metropolitan Melbourne. Participants were recruited into the study using purposive and snowball sampling techniques. RESULTS: Most (88%; 550/625) children had never visited the dentist (mean (SD) age 3.06 years (1.11)). In the fully adjusted model the variable most significantly associated with child dental visiting was parent reported 'no reason for child to visit the dentist' (OR = 0.07, p < 0.001). Of those children whose parents reported their child had no reason to visit the dentist, 22% (37/165) experienced dental caries with 8% (13/165) at the level of cavitation. CONCLUSIONS: Dental service use by migrant preschool children was very low. The relationship between perceived dental need and dental service use is currently not aligned. One in 10 children of select migrant background had visited a dentist, which is in the context of 1 in 3 with dental caries. To improve utilization, health services should consider organizational cultural competence, outreach and increased engagement with the migrant community.

Investigating the effect of silver coating on the solubility, antibacterial properties, and cytocompatibility of glass microspheres.

Silver (Ag) coatings have been incorporated into many medical materials due to its ability to eradicate harmful microbes. In this study, glass microspheres (SiO2-Na2O-CaO-Al2O3) were synthesized and employed as substrates to investigate the effect Ag coating has on glass solubility and the subsequent biological effects. Initially, glasses were amorphous with a glass transition point (T(g)) of 605℃ and microspheres were spherical with a mean particle diameter of 120 µm (±27). The Ag coating was determined to be crystalline in nature and its presence was confirmed using scanning electron microscopy and X-ray photoelectron spectroscopy. Ion release determined that Ag-coated (Ag-S) microspheres increased the Na(+) release rate but slightly reduced the Ca(2+) and Si(4+) release compared to an uncoated control (UC-S). Additionally, the Ag-S reduced the pH to just above neutral (7.3-8.5) compared to the UC-S (7.7-9.1). Antibacterial testing determined significant reductions in planktonic Escherichia coli (p = 0.000), Staphylococcus epidermidis (p = 0.000) and Staphylococcus aureus (p = 0.000) growth as a function of the presence of Ag and with respect to maturation (1, 7, and 30 days). Testing for toxicity levels using L929 Fibroblasts determined higher cell viability for the Ag-S at lower concentrations (5 µg/ml); in addition, no significant reduction in cell viability was observed with higher concentrations (15, 30 µg/ml).

Changes in the molecular composition of circulating hydroxyethyl starch.

1. Hydroxyethyl starch (HES) of molecular weight 450,000 has been extensively investigated as a plasma volume expander and HES of molecular weight 60,000 has been proposed for use as a cryoprotective agent in the freezing for preservation of red blood cells. In these applications considerable amounts of HES may be injected intravenously and it is therefore desirable to understand its behaviour in vivo.2. After intravenous injection into rabbits, plasma levels of HES and clinical dextrans were determined using anthrone. HES persisted longer in the circulation than did the dextrans.3. HES was recovered from the bloodstream of rabbits and shown by gel filtration to be of a narrower molecular size distribution than the injected material. Smaller molecules were removed, presumably by filtration at the glomerulus. Larger molecules may have been removed by cells of the reticuloendothelial system or possibly through the action of amylase.4. The amylase in saliva was shown to break down HES into molecules of intermediate size with very little production of maltose units.

Chronic treatment with clozapine, unlike haloperidol, does not induce changes in striatal D-2 receptor function in the rat.

Comparison has been made of the effects on brain dopamine function of chronic administration of haloperidol or clozapine to rats for up to 12 months. In rats treated for 1-12 months with haloperidol (1.4-1.6 mg/kg/day), purposeless chewing jaw movements emerged. These movements were only observed after 12 months' treatment with clozapine (24-27 mg/kg/day). Apomorphine-induced (0.125-0.25 mg/kg) stereotyped behaviour was inhibited during 12 months treatment with haloperidol. Clozapine treatment was without effect. After 12 months, stereotypy induced by higher doses of apomorphine (0.5-1.0 mg/kg) was enhanced in haloperidol, but not clozapine, treated rats. Bmax for striatal 3H-spiperone binding was elevated throughout 12 months of haloperidol administration, but was not altered by clozapine treatment. Bmax for striatal 3H-NPA binding was only elevated after 12 months of haloperidol treatment; clozapine treatment was without effect. Bmax for 3H-piflutixol binding was not altered by haloperidol treatment, but was increased after 9 and 12 months of clozapine treatment. Dopamine (50 microM)-stimulated adenylate cyclase activity was inhibited after 1 month's haloperidol treatment but normal thereafter. Adenylate cyclase activity was not altered by chronic clozapine treatment. Striatal acetylcholine content was increased after 3 and 12 months of haloperidol or clozapine intake. These findings indicate that the chronic administration of the atypical neuroleptic clozapine does not produce changes in brain dopamine function which mirror those of the typical neuroleptic haloperidol. In particular, chronic administration of clozapine, unlike haloperidol, does not appear to induce striatal D-2 receptor supersensitivity. Unexpectedly, clozapine treatment, unlike haloperidol, altered D-1 receptor function.

Lymphocyte response to silica among offspring of silicone breast implant recipients.

The current study evaluated immune response to silicon dioxide in children born to women with silicone breast implants. In part one of the study, the T lymphocytes of 21 of 24 such children were significantly stimulated by silicon dioxide (silica). Part two consisted of eleven children, four born preimplantation and seven born postimplantation. None of the preimplant offspring showed T cell responses to silica; five of the seven postimplant children were positive for T cell memory for silica. Part three was a blinded study based on statistically significant differences in T cell stimulation with silicon dioxide between postimplant children and controls. These findings indicate a common immune reaction, that of T cell memory, occurs in mothers and their children born after exposure to silicone mammary implants placed prior to pregnancy. Since not all such children were breast fed the result favors transplacental passage of immunogens such as silicone oligomers or through maternofetal cellular traffic.

Differential effects of continuous administration for 1 year of haloperidol or sulpiride on striatal dopamine function in the rat.

Administration of haloperidol (1.4-1.6 mg/kg/day) for up to 12 months or sulpiride (102-109 mg/kg/day) for between 6 and 12 months increased the frequency of purposeless chewing jaw movements in rats. N,n-propylnorapomorphine (NPA) (0.25-2.0 mg/kg SC) did not induce hypoactivity in haloperidol-treated rats at any time; sulpiride treatment for 9 and 12 months caused a reduction in the ability of NPA to induce hypoactivity. Haloperidol, but not sulpiride, treatment enduringly inhibited low dose apomorphine effects (0.125 mg/kg SC). After 12 months, stereotypy induced by high doses of apomorphine (0.5-1.0 mg/kg) was exaggerated in haloperidol-, but not sulpiride-treated rats. Bmax for specific striatal 3H-spiperone binding was increased by haloperidol, but not sulpiride, treatment throughout the study. Bmax for 3H-piflutixol binding was not altered by chronic haloperidol or sulpiride treatment. Striatal dopamine-stimulated adenylate cyclase activity was inhibited for the 1st month of haloperidol treatment, thereafter returning to control levels; dopamine stimulation was increased after 12 months of sulpiride treatment. Striatal acetylcholine content was increased after 3 and 12 months of treatment with haloperidol, but was not affected by sulpiride. Chronic administration of sulpiride does not induce identical changes in striatal dopamine function to those caused by haloperidol.

The role of interval underestimation in hyperactive children's failure to suppress responses over time.

The relationship between response inhibition and time estimation abilities was investigated in a group of hyperactive and non-hyperactive children. Children performed a discrete trials intertemporal response task under two conditions. Under both conditions children had to respond within a 2 s window, which was delayed for a set period (either 5 or 15 s). In condition one (signalled condition), these response requirements were signalled by changes in the expression of a face drawn on a computer screen. In condition two (unsignalled condition), always presented on the trial following the signalled condition, these changes in expression were obscured by a hand drawn over the mouth of the face so that effective performance depended on the childs ability to estimate the point at which the facial expression changed on the preceding trial. Both groups of children had little difficulty inhibiting responses when the response requirements were signalled. All children made far more errors under the unsignalled condition. Hyperactive children displayed a systematic tendency to respond before the response window occurred. Taken together, these data give no support to the idea that hyperactivity is essentially a problem of disinhibition and raise interesting questions about the role of time mis-estimation in the disorder.