(-)-Stepholidine blocks expression, but not development, of cocaine conditioned place preference in rats.

The purpose of this study was to investigate the effects of (-)-stepholidine (SPD), a compound with dopamine D1 partial agonist and D2/D3 antagonist properties, on the development and expression of cocaine conditioned place preference (CPP). Subjects (N = 65; male Long Evans rats) were tested using a CPP procedure consisting of 3 phases: (1) a 15-min pre-exposure session where animals could explore each compartment freely, (2) eight 30-min conditioning sessions where animals were restricted to one side or the other with cocaine (10 mg/kg) or saline, respectively, on alternating days and (3) a 15-minute preference test session where animals could explore each compartment freely. To test the effects of SPD on expression of cocaine CPP, rats were administered vehicle (distilled water with 20 % DMSO), 10, 15 or 20 mg/kg SPD (intraperitoneally) 30 min prior to the test session. We found that 20 mg/kg of SPD significantly blocked the expression of cocaine CPP. To test the effects of SPD on the development of CPP, 0 (vehicle), 10, 15 or 20mg/kg SPD were administered 30 min prior to each cocaine conditioning session and vehicle before each saline conditioning session; no treatment was given prior to the test session. A preference test showed that each SPD group maintained a CPP similar to the vehicle group. These data indicate that SPD can block the expression of a cocaine CPP but has no effect on its development, suggesting that it inhibits the effects of cocaine cues on cocaine incentive motivated behavior. These results suggest that SPD may be a potential treatment for cue-driven aspects of cocaine use disorder.

(-)-Stepholidine reduces cue-induced reinstatement of cocaine seeking and cocaine self-administration in rats.

BACKGROUND: Dopamine receptors are implicated in cocaine reward and seeking. We hypothesize that (-)-stepholidine, a dopamine D1/D2/D3 multi-receptor agent, would be effective in reducing cocaine reward and seeking in an animal model. We investigated the effects of (-)-stepholidine in cue-induced reinstatement of cocaine seeking and cocaine self-administration (reward). METHODS: Cue-induced reinstatement experiment: Rats were trained to press a lever reinforced by cocaine (1 mg/kg/injection) for 15 consecutive daily sessions, after which the response was extinguished by withholding cocaine and cocaine-paired cues (light and pump activation). This was followed by a cue-induced reinstatement test where subjects were exposed to two cocaine cue presentations and presses on the active lever produced cues. Subjects were treated with one of four (-)-stepholidine doses prior to the reinstatement test. Cocaine self-administration (reward) experiment: Rats were trained to self-administer cocaine under a progressive ratio schedule of reinforcement. After stable breakpoints were established, rats were injected with four doses of (-)-stepholidine prior to testing; each dose was injected prior to a separate test session with no-treatment sessions intervening to re-establish break points. RESULTS: (-)-Stepholidine significantly reduced cue-induced reinstatement of cocaine seeking in a dose-related manner. Additionally, (-)-stepholidine significantly reduced break points for cocaine reward. (-)-Stepholidine did not significantly affect locomotor activity. CONCLUSIONS: (-)-Stepholidine reduces cue-induced reinstatement of cocaine seeking and cocaine reward, suggesting that it may be useful in treating relapse in cocaine addiction.

Dopamine D1 and D3 receptor interactions in cocaine reward and seeking in rats.

RATIONALE: Animal research has demonstrated a role of dopamine D1 and D3 receptors in cocaine reward and seeking. PURPOSE AND METHODS: Here, we investigated the potential interaction of these two dopamine receptors in cue-induced reinstatement of cocaine seeking, cocaine conditioned place preference (CPP), and cocaine self-administration in rats. RESULTS: The co-administration of a D3 receptor antagonist, NGB 2904 and a D1 partial agonist, SKF 77434, of doses which when administered individually produced no significant effects, prior to reinstatement or CPP tests significantly reduced lever pressing and time spent in the cocaine-paired environment, suggesting synergistic effects of the combined compounds on cocaine seeking. When given to rats self-administering cocaine under a progressive ratio schedule of reinforcement doses of NGB 2904 which were ineffective alone significantly enhanced the break point-reducing effects of SKF 77434. CONCLUSIONS: Our results indicate that the combined treatment with a D1 receptor partial agonist and D3 receptor antagonist produces robust decreases in cocaine seeking and reward. This suggests an interaction between dopamine D1 and D3 receptors in cocaine-related behaviors.

Organochlorine pesticide levels in Clarias gariepinus from polluted freshwater impoundments in South Africa and associated human health risks.

There are increasing concerns regarding the safe human consumption of fish from polluted, freshwater impoundments. The aim of this study was to analyse the muscle tissue of the sharptooth catfish Clarias gariepinus for selected organo-chlorine pesticides (OCPs) and to perform a human health risk assessment using a standard protocol described by the United States Environmental Protection Agency (US EPA). Fish were collected from the polluted Roodeplaat-(RDPD), Rietvlei-(RVD) and Hartbeespoort (HBPD) Dam impoundments located in the north-eastern regions of South Africa. GC-MS analyses showed levels of various OCPs in fish muscle samples from all three impoundments. For fish collected from the RDPD, p,p'-DDE, endosulfan, lindane and ß- and δ-HCH were the most prevalent OCPs detected, while p,p'-DDE and endosulfan were the most predominant in fish from the RVD. Lindane and ß- and δ-HCH were the main OCPs detected in fish from the HBPD. Dieldrin was the only OCP detected at concentrations for which a cancer risk and a hazard index above the acceptable risk levels were estimated. This was the case for fish from both the RDPD and RVD impoundments. No toxic risk was estimated should fish from the HBPD be consumed.

Conjugal transfer of a virulence plasmid in the opportunistic intracellular actinomycete Rhodococcus equi.

Rhodococcus equi is a facultative intracellular, Gram-positive, soilborne actinomycete which can cause severe pyogranulomatous pneumonia with abscessation in young horses (foals) and in immunocompromised people, such as persons with AIDS. All strains of R. equi isolated from foals and approximately a third isolated from humans contain a large, ~81-kb plasmid which is essential for the intramacrophage growth of the organism and for virulence in foals and murine in vivo model systems. We found that the entire virulence plasmid could be transferred from plasmid-containing strains of R. equi (donor) to plasmid-free R. equi strains (recipient) at a high frequency and that plasmid transmission reestablished the capacity for intracellular growth in macrophages. Plasmid transfer required living cells and cell-to-cell contact and was unaffected by the presence of DNase, factors pointing to conjugation as the major means of genetic transfer. Deletion of a putative relaxase-encoding gene, traA, located in the proposed conjugative region of the plasmid, abolished plasmid transfer. Reversion of the traA mutation restored plasmid transmissibility. Finally, plasmid transmission to other Rhodococcus species and some additional related organisms was demonstrated. This is the first study showing a virulence plasmid transfer in R. equi, and it establishes a mechanism by which the virulence plasmid can move among bacteria in the soil.

An opioid agonist that does not induce mu-opioid receptor--arrestin interactions or receptor internalization.

G protein-coupled receptor desensitization and trafficking are important regulators of opioid receptor signaling that can dictate overall drug responsiveness in vivo. Furthermore, different mu-opioid receptor (muOR) ligands can lead to varying degrees of receptor regulation, presumably because of distinct structural conformations conferred by agonist binding. For example, morphine binding produces a muOR with low affinity for beta-arrestin proteins and limited receptor internalization, whereas enkephalin analogs promote robust trafficking of both beta-arrestins and the receptors. Here, we evaluate muOR trafficking in response to activation by a novel mu-selective agonist derived from the naturally occurring plant product, salvinorin A. It is interesting that this compound, termed herkinorin, does not promote the recruitment of beta-arrestin-2 to the muOR and does not lead to receptor internalization. Moreover, whereas G protein-coupled receptor kinase overexpression can promote morphine-induced beta-arrestin interactions and muOR internalization, such manipulations do not promote herkinorin-induced trafficking. Studies in mice have shown that beta-arrestin-2 plays an important role in the development of morphine-induced tolerance, constipation, and respiratory depression. Therefore, drugs that can activate the receptor without recruiting the arrestins may be a promising step in the development of opiate analgesics that distinguish between agonist activity and receptor regulation and may ultimately lead to therapeutics designed to provide pain relief without the adverse side effects normally associated with the opiate narcotics.

Management of a simple anterior crossbite in a child with autism: a review and case report.

This case report describes a simple treatment used to correct an anterior crossbite in a child with autism. A review of autism and the treatment of simple anterior crossbite are given. It is possible for children with special needs to be managed in the general practice setting, although treatment plans may need to be modified to meet the capabilities of individual patients. Follow-up is required for cases of anterior crossbite treated in the early mixed dentition.

Do drivers drink more when they use a safe ride?

PURPOSE: Offering drinkers free safe rides (SRs) home can prevent DWI, but some suggest that it may also promote excessive drinking. METHODS: Forty-two respondents to surveys completed by 472 drinkers in barrooms reported that they used a SR during the first 9 months they were offered. RESULTS: Their usual estimated blood alcohol concentration (BAC) was significantly greater when they used a SR than on all occasions when they drank outside their homes. However, only 24% of respondents increased their usual BAC from a " low risk" category (BAC <0.10) when drinking outside the home, to a "high risk" category (BAC > or = 0.10) when using a SR. The majority (72%) of respondents did not change their BAC categories. One decreased his/her BAC from > or = 0.10 when drinking outside the home to <0.10 when using a SR. IMPLICATIONS: These findings, coupled with data showing that respondents tended to use SRs infrequently (3.69 times per year), reduce concerns about the mean increase in their BACs when using SRs. Findings do not, however, resolve the issue of whether respondents whose drinking increased when they used a SR did so because a SR was available, or decided not to drive because they drank more. Recommendations for improving SR programs are discussed.

The delivery of orthodontic care in New Zealand. Part I: Analysis of a census of orthodontists.

A two-part study was undertaken to determine the supply of orthodontic services in New Zealand. Part I focuses on services supplied by specialist orthodontists. A companion paper will describe the amount and characteristics of orthodontic services supplied by dentists. All orthodontists in New Zealand in 1999 were surveyed to provide information on practice location and days practiced in 1996 (the year of the last population Census), and the amount and type of orthodontic treatment carried out in the year 1 July 1998 to 30 June 1999. The response rate was 78.9 percent. Data from 1996 were used to establish and quantify the location and distribution of orthodontists in New Zealand, and their spatial relationship to 12-year-olds and 10- to 14-year-olds using Geographic Information Systems. The information from 1998-1999 was used to determine the amount and variety of services provided by orthodontists and the makeup of their patient base. Nearly two-thirds of orthodontists had a branch practice. Over 50 percent of the 10- to 14-year-old population resided within 5 km of an orthodontist, and nearly three-quarters within 10 km. Disparities between regions existed in the supply of specialist orthodontic services. The catchment areas of main urban areas had more than three times the supply of orthodontists to 12-year-olds than did the secondary and minor urban areas combined. The mean average active patient load was 371, and the mean number of full upper and lower fixed appliances placed was 130.3 during the year of the study. Nearly half of all patients had been referred from dentists, approximately one-quarter were self-referred, and a quarter had been referred by dental therapists. Adults comprised 12.1 percent of the patient load of orthodontists; 60 percent were female.

New diterpenes from Jatropha divaricata.

Extracts of the stems of Jatropha divaricata have yielded the two new diterpenes ent-3 beta,14 alpha-hydroxypimara-7,9(11),15-triene-12-one (3) and the rearranged pimarane ent-15(13-->8)abeo-8 beta(ethyl)pimarane (4), which appears to be a new skeletal type. The rare cleistanthane diterpenes spruceanol (1) and cleistanthol (2) were also obtained.

DWI prevention: profiles of drinkers who use designated drivers.

The effectiveness of designated driver (DD) use in preventing driving while intoxicated (DWI) depends on whether drinkers at risk for DWI use DDs. Bivariate and logistic regression analyses conducted on data from 1,391 Computer-Assisted Telephone Interviews (CATIs) and from 902 barroom patron surveys showed that DD users, compared to nonusers, tended to be at-risk, heavier drinkers. For example, logistic regression using the CATI sample indicated that DD users were more likely to drink more often outside the home, to achieve higher blood alcohol concentrations (BACs) when drinking outside the home, to ride with intoxicated drivers (RID), and to be heavy drinkers on D. Cahalan et al.'s (1969) Quantity-Frequency-Variability (QFV) index. Similarly, logistic regression using the barroom sample showed that DD users tended to be heavy drinkers on the QFV index, and were more likely to drive after drinking and to ride with intoxicated drivers. Additional analyses showed that DD users also were more likely than nonusers to engage in other behavior to avoid DWI, such as drinking less, waiting to drive until the effects of alcohol diminish, walking home, and staying overnight. These results are consistent with other findings from a related study by the current authors which showed that at-risk drinkers also used free safe (taxi) rides to avoid DWI, however were still more likely to report DWI and RID behavior (B. D. Caudill, W. M. Harding, & B. Moore, in press). Consequently, DWI prevention efforts may be improved by future research aimed at learning why such at-risk drinkers sometimes take steps to avoid DWI and sometimes do not.

Complete arthroscopic examination of the long head of the biceps tendon.

We describe an arthroscopic technique that allows complete examination of the long head of the biceps tendon. Important additional information during arthroscopic examination of the shoulder can be obtained by including inspection of the intertubercular portion of the tendon. Failure to inspect this portion of the tendon may lead to an unsuccessful and frustrating postoperative course for both the patient and physician.

Do companions of designated drivers drink excessively?

PURPOSE: A common criticism of designated driver programs (DDPs) is that they promote excessive drinking among companions of the designated driver (DD). METHODS: Data were collected from two representative samples of drinkers using computer-assisted telephone interviews (CATIs), and questionnaires administered to customers in barrooms. RESULTS: Most respondents drank moderately--had usual estimated blood alcohol concentrations (BACs) of less than 0.10 when they used DDs. Differences between respondents' estimated BACs when they used a DD and when they drank outside their homes were very small: 0.017 in both samples. Additional analyses examined shifts between lower and higher categories of risk defined as a BAC of less than 0.10 and a BAC of 0.10 or greater. A minority, 15% of CATI and 30% of barroom respondents, switched to the higher risk category when using a DD. These CATI and barroom respondents increased their BACs by an average of 0.089 and 0.11, respectively. Risk associated with this increase was mitigated, however, by respondents' infrequent use of DDs. IMPLICATIONS: Use of DDs was not generally associated with excessive alcohol consumption. Since a minority of respondents did drink heavily when using a DD, programs promoting DD use should caution drinkers that the availability of a DD is not an excuse for excessive consumption, and remind hosts and servers that they should not overserve their guests or customers even when they have a DD.

Cycloartanes, protolimonoids, a pregnane and a new ergostane from Trichilia reticulata.

The new ergostane steroid ergosta-5,24(24')-diene-3beta,4beta,22R-triol (1), a pregnane, (E)-volkendusin, characterised as the diacetate (3), cycloartanes 4-6 and protolimonoids 7-9 were obtained from the leaves and twigs of Trichilia reticulata.

The delivery of orthodontic care in New Zealand. Part II: Analysis of a census of dentists.

Part I of this study reported the level and distribution of the supply of specialist orthodontic services in New Zealand. This paper focuses on the amount and variety of orthodontic services supplied by dentists. A questionnaire sent to all dentists in New Zealand sought information on the amount and type of orthodontic treatment carried out between 1 July 1998 and 30 June 1999. The reply rate was 80.9 percent. The majority of dentists carried out some form of orthodontic treatment, predominantly of a minor nature. A small number provided significant amounts of treatment, both simple and complex. The majority of orthodontic treatment and the majority of comprehensive fixed-appliance treatment were undertaken by orthodontists. One-quarter of all orthodontic patients in New Zealand were treated by dentists, irrespective of the complexity of treatment. Nearly a fifth of all full fixed upper and lower appliances, and nearly a third of all single-arch fixed appliances were placed by dentists during the study period. In general, male dentists, dentists over the age of 40, those who had attended an orthodontic continuing education course in the previous 5 years, and those who referred fewer patients to an orthodontist carried out more procedures, including those of a complex nature; they also had a higher average active orthodontic patient load. Wanting to be more or less busy had little influence on the amount or complexity of treatment performed. Dentists in regions with a low supply of specialist orthodontic services provided more comprehensive fixed appliance treatment and had a higher orthodontic patient load. However, the presence or absence of an orthodontist in an urban area seemed to have little impact on the complexity of treatment or the orthodontic patient load of dentists. Despite fewer orthodontists in secondary and minor urban areas, dentists in these areas did not have a higher orthodontic patient load, but carried out a wider range of procedures and more complex procedures than those in main urban areas.

At-risk drinkers use safe ride services to avoid drinking and driving.

PURPOSE: A central question pertinent to the efficacy of safe rides (SRs) in preventing driving while intoxicated (DWI) is whether individuals at high risk for DWI use them. METHODS: Barroom surveys (N = 472) and in situ breath tests (N = 51) were conducted as part of an assessment of an alternative transportation intervention in a Maryland community. Bivariate analyses and stepwise logistic regression were performed comparing 42 barroom respondents who reported using a SR in the last 12 months to non-users. RESULTS: Bivariate analyses showed that SR users drank more frequently outside the home and achieved higher estimated blood alcohol concentrations (BACs) when they did. Also, they were more likely to be heavy drinkers, to have driven when feeling intoxicated, and to have been arrested for DWI. Although SR users were more likely to ride with an intoxicated driver, they were also more likely to use a designated driver (DD). Stepwise logistic regression showed SR users were more likely to be heavy drinkers and to use DDs. In situ breath test data showed SR users' BACs ranged from 0.031 to 0.248, with a mean of 0.146. IMPLICATIONS: SR programs attract drinkers at high risk for DWI. DWI prevention efforts would benefit from future research exploring how at-risk drinkers make drinking and driving decisions.

DWI prevention: profiles of drinkers who serve as designated drivers.

This study was designed to profile drinkers who serve as designated drivers (DDs) and to determine if drinkers who are at risk for driving while intoxicated (DWI) serve as DDs. Bivariate and logistic regression analyses on data from 1,393 computer-assisted telephone interviews (CATIs) and 913 bar-room surveys showed that DDs, relative to non-DDs, tend to be at-risk, heavier drinkers. Logistic regression using CATI data showed that DDs were more often heavy drinkers and reported higher levels of driving after drinking and riding with intoxicated drivers (RID). Logistic regression using bar-room data showed that DDs reported more driving after drinking, in spite of drinking less often outside the home. DDs were also much more likely to have used a DD. These findings are consistent with those from several related studies that showed that drinkers who used DDs or free safe (taxi) rides tended to be heavier drinkers who reported more DWI and RID (B. D. Caudill, W. M. Harding, & B. Moore, in press-a, in press-b). Future research may benefit from examining why at-risk drinkers take steps to avoid DWI on some occasions but not others.

The scapulohumeral line revisited.

Routine observation of the scapulohumeral line in the true anteroposterior radiographic view of the shoulder will allow a higher level of confidence in ruling out posterior dislocation of the glenohumeral joint. It will also facilitate evaluation of the relationship between the proximal humerus and the scapula (especially the acromion and the glenoid fossa) in (1) abnormal conditions of the subacromial space; (2) fractures and dislocations of the proximal humerus; and (3) proximal humerus prosthesis insertion and assessment.

Using research in community nursing.

The concept of evidence-based medicine has received considerable attention, but the distinctive nature of evidence within community nursing has not been fully explored. This study examines the nature of evidence within community nursing and the factors influencing use of evidence. Although much of the literature has concentrated on individuals as sites of resistance to evidence-based change, the findings of this study suggest that organisational and cultural factors represent more significant obstacles.

Plane talk about shoulder radiographs.

The evaluation of patients who have pain, loss of motion, instability, or weakness in the shoulder is often enhanced by x-ray assessment. A common approach to radiographic examination of the shoulder is to take two anteroposterior (AP) views, one with the humerus in external rotation and one with the humerus in internal rotation.