The osteogenic potential of the marine-derived multi-mineral formula aquamin is enhanced by the presence of vitamin D.

Bone degenerative diseases are on the increase globally and are often problematic to treat. This has led to a demand to identify supplements that aid bone growth and formation. Aquamin is a natural multi-mineral food supplement, derived from the red algae Lithothamnion species which contains calcium, magnesium and 72 other trace minerals. It has been previously reported to increase bone formation and mineralisation. This study aimed to investigate the 28 day in vitro osteogenic response of Aquamin supplemented with Vitamin D. The osteogenic potential of MC3T3-E1 osteoblast-like cells was analysed in standard osteogenic medium supplemented with Aquamin +/- Vitamin D3, and the controls consisted of osteogenic medium, +/- Vitamin D3. Proliferation of osteoblasts, metabolic activity and cell viability did not differ between Aquamin and the osteogenic control groups. Alkaline phosphatase (ALP) levels and mineralisation were increased by the supplementation of Aquamin, and the addition of Vitamin D3 increased mineralisation for all groups. The combination of Aquamin and Vitamin D3 yielded a significant increase in ALP and mineralisation over Aquamin alone and the standard osteogenic control +/- Vitamin D3. This study demonstrates that Aquamin aids osteogenesis, and that its osteogenic response can be enhanced by combining Aquamin with Vitamin D3.

Cloning of an interleukin-3 receptor gene: a member of a distinct receptor gene family.

Interleukin-3 (IL-3) binds to its receptor with high and low affinities, induces tyrosine phosphorylation, and promotes the proliferation and differentiation of hematopoietic cells. A binding component of the IL-3 receptor was cloned. Fibroblasts transfected with the complementary DNA bound IL-3 with a low affinity [dissociation constant (Kd) of 17.9 +/- 3.6 nM]. No consensus sequence for a tyrosine kinase was present in the cytoplasmic domain. Thus, additional components are required for a functional high affinity IL-3 receptor. A sequence comparison of the IL-3 receptor with other cytokine receptors (erythropoietin, IL-4, IL-6, and the beta chain IL-2 receptor) revealed a common motif of a distinct receptor gene family.

The creation of evidence in 'evidence-based' drug prevention: a critique of the Strengthening Families Program Plus Life Skills Training evaluation.

School-based curricula have become a mainstay of drug prevention policy in the United States and are increasing in popularity in other parts of the world. The promotion and dissemination of these interventions has been driven in large part by the creation of lists of programmes which, it is claimed, are grounded in scientific evidence demonstrating their effectiveness. Recently concerns have been raised about the data analysis and presentation practices used in evaluations of a number of programmes that appear on these lists. Here we examine a series of papers from an evaluation of an intervention that combined the Strengthening Families Program 10-14 and Life Skills Training Program, each of which is among the most widely advocated universal drug prevention programmes. The data analysis and presentation practices employed in the evaluation of this combined programme include one-tailed significance testing, alpha levels of 0.10, changes in outcome variables across publications and use of the post-test data as the baseline when assessing change over time. Taken together, these practices severely limit the claims that can be made about the results presented in the evaluation. Specifically, we believe that far from supporting the evaluators' claims concerning the rigour of the findings and their generalisability and public health significance, the results are very fragile, of little practical significance and quite possibly analysis-dependent.

Molecular signals in anti-apoptotic survival pathways.

Drug resistance, to date, has primarily been attributed to increased drug export or detoxification mechanisms. Despite correlations between drug export and drug resistance, it is increasingly apparent that such mechanisms cannot fully account for chemoresistance in neoplasia. It is now widely accepted that chemotherapeutic drugs kill tumour cells by inducing apoptosis, a genetically regulated cell death programme. Evidence is emerging that the exploitation of survival pathways, which may have contributed to disease development in the first instance, may also be important in the development of the chemoresistance. This review discusses the components of and associations between multiple signalling cascades and their possible contribution to the development of neoplasia and the chemoresistant phenotype.

Sensitisation of HL60 human leukaemic cells to cytotoxic drug-induced apoptosis by inhibition of PI3-kinase survival signals.

Drug resistance remains a serious limiting factor in the treatment of acute myeloid leukaemia (AML) either at initial presentation or following primary or subsequent relapses. Using specific kinase inhibitors, this study has investigated the contribution of the Ras/PI3-kinase regulated survival pathways to drug resistance and suppression of apoptosis in a cell line derived from AML (HL60). Inhibition of the Raf/MAP-kinase (ERK) pathway with a specific MAP-kinase inhibitor, apigenin did not sensitise HL60 cells to drug-induced apoptosis, indicating a lack of involvement in chemoresistance. In contrast, the PI3-kinase inhibitors, LY294002 and wortmannin, did induce a significant increase in apoptosis in combination with cytotoxic drugs. The contribution of downstream mediators of PI3-kinase, p70S6-kinase and PKB/Akt were then investigated. While inhibition of p70S6-kinase with rapamycin did not increase drug-induced apoptosis, PI3-kinase inhibition resulted in notable dephosphorylation of PKB, suggesting that the PI3-kinase/PKB survival pathway may play a major role in chemoresistance in AML. This pathway has been reported to mediate heterodimer interactions with the proapoptotic regulator, Bad. In contrast to previous studies, we found no evidence of Bad binding to anti-apoptotic Bcl-2, Bcl-XL or McI-1, or of alterations in Bax heterodimers. This suggests that alternative targets of PI3-kinase/PKB, distinct from the Bcl-2 family may be responsible for contributing to survival factor-mediated drug resistance in AML.

Drug 'hot-spots', alcohol availability and violence.

Ecological studies have shown a relationship between alcohol outlet densities and violence and between the location of crimes related to illicit drug use (so-called 'hot spots') and violence. To date, no study has compared the effects of alcohol outlets and drug hot spots on rates of violence. The present study examined this relationship in the City of Houston, Texas. An ecological study design was employed, using a sample of 439 census tracts from Houston, Texas. Neighborhood socio-structural, alcohol outlet density, drug crime density and violent crime density data were collected from archival sources and analyzed using multivariate and spatial statistics. Using ordinary least-squares analysis, the neighborhood socio-structural covariates explained about 40% of the variability in violent crime. Adding alcohol outlet density in the target census tracts explained an additional 6%, while the addition of drug crime density explained an additional 32%. In the final model, that controlled for the effects of autocorrelated error, both drug crime density in the target and adjacent census tracts remained significant predictors of violent crime, while only off-sale density in the target census tract remained significant in the model. The findings indicate that drug crime density explained a greater amount of variance in violent crime rates than the alcohol outlet density. The methodological and policy implications of these findings are discussed, along with the shortcomings of the analysis presented.

Applications of retrovirus-mediated expression cloning.

We have recently established a novel expression cloning system using retroviral vectors. The system is based on a high-efficiency packaging cell line, BOSC23, and a simplified retroviral vector, pBabeX, carrying no selection marker. cDNA libraries, constructed in the pBabeX vector, are transiently transfected into BOSC23 cells. The supernatant contains more than 3X10(6)/mL, which would cover large complexities of cDNA libraries. The retrovirus stock gave 100% infection efficiency in NIH3T3 cells and 5-40% infection efficiency in various hematopoietic cell lines. In contrast to the conventional expression cloning system, in which it is necessary to transfect cDNA libraries transiently into particular cell types such as COS cells, retrovirus-mediated expression cloning allows us to transduce cDNAs into a wide variety of cell types. This method therefore makes it possible to select cells expressing a cDNA of interest by various functional assays. When combined with polymerase chain reaction (PCR)-driven random mutagenesis, this system is also useful in searching for mutations of various molecules that will result in alterations of their functions.

Inhibition of PI3-kinase sensitises HL60 human leukaemia cells to both chemotherapeutic drug- and Fas-induced apoptosis by a JNK independent pathway.

Increasing resistance to chemotherapeutic regimes remains a serious problem in the treatment of acute myeloid leukaemia. We have shown that phosphatidylinositol (PI) 3-kinase inhibition significantly sensitises the AML derived cell line, HL60 to chemotherapeutic drug- and Fas-induced apoptosis. PI3-kinase inhibition significantly potentiates cytotoxic drug-induced c-jun N-terminal kinase (JNK) activation, reported to be a requirement for apoptosis. However, JNK inhibition does not enhance cell viability following treatment with drug and inhibitor. Furthermore, PI3-kinase inhibition significantly increases sensitivity to apoptosis mediated by an exogenous receptor agonist, again by a JNK independent mechanism. These results suggest that PI3-kinase inhibitors could be of significant therapeutic importance, lowering the threshold for apoptosis induced by both chemotherapy and cell-mediated immune response.

A theory-driven approach to the evaluation of professional training in alcohol abuse.

This paper begins by observing that, to date, evaluations of brief training courses in alcohol abuse for non-specialist professionals indicate that they have little influence on attitudes and behaviour. The reasons why this is so have not been studied in detail, and such training courses continue to be widely used despite their minimal effects. It is argued that the failure of this field of inquiry to develop beyond this point is due to the fact that, with only a very few exceptions, it has not been informed by theoretical concerns. The research in this area is discussed in terms of the types of models tested and the research designs typically used in evaluations. This is followed by a detailed description of the 'theory driven approach' to evaluation. It is proposed that the use of such an approach by those concerned with the development and evaluation of training in alcohol abuse for non-specialists would increase the likelihood of identifying the real effects of such programmes and the processes that mediate their successful implementation. This would result in a more purposeful use of educators' and evaluators' energies and skills.

Employment, stressful life events and the development of alcohol dependence.

Features of employment structures and occupational environments are considered to increase risk of alcohol dependence amongst both males and females, although the mechanisms whereby this operates are not clearly understood. The present retrospective case-control study examined the way in which factors related to employment and occupation facilitated the development of alcohol dependence following the occurrence of a stressful life event. Results showed that for males, there were certain occupational risk factors that were conducive to the development of alcohol dependence, and that risk was especially high for those working in such occupations who experienced a stressful event. For females, there was some evidence to suggest that full-time employment increased risk of alcohol dependence, at least for married women. It is suggested that, in order to better understand the factors of employment conducive to the development of female alcohol dependence, measures focussed specifically on work environments, such as those used in the present study of males should be developed.

Level of agreement between questionnaire measures of alcohol dependence, alcoholism and problem drinking in a sample presenting at a specialist alcohol treatment service.

Two questionnaire measures of the alcohol dependence syndrome, one of alcoholism, and one of alcohol-related problems were compared in a sample of 101 subjects attending a specialist alcohol treatment unit. There was substantial agreement between the two measures of alcohol dependence, and lesser agreement between any other pairing. The measures of alcohol dependence also showed the strongest correlation with reported weekly alcohol consumption. The findings are compared with previous research, and the suitability of the various questionnaires as case-defining instruments in empirical investigations is discussed.

Using social indicators to inform community drug and alcohol prevention policy.

In recent years, the federal government has begun to require state agencies to allocate drug prevention resources according to the needs of local communities. The methods by which this is to be accomplished have not been described, and most published social indicator studies in the field of drug abuse research have used county-level data which are too insensitive to local needs to be of use in resource allocation decisions. The present study describes a needs assessment in drug abuse prevention in the state of New Jersey using municipal-level social indicator data. In addition, it examines the extent to which the resource allocation of one state prevention agency can be predicted by the municipal-level social indicators. Thirty-six social indicators pertaining to 508 municipalities were used in the study, and data were analyzed using principal component analysis and hierarchical regression analysis. Five factors were extracted from the principal component analysis, two of which clearly describe "high risk" municipalities and one of which clearly describes "low risk" municipalities. The regression analysis showed that these factors explained very little of the variance in the state agency's drug prevention spending. The study shows that social indicators can be used to distinguish between different levels of need for drug prevention services at a municipal level, and that these data can be used to inform decisions concerning resource allocation.

Violent crime and alcohol availability: relationships in an urban community.

The relationship between violent crime, neighborhood sociodemographic characteristics, and alcohol outlet densities in Newark, New Jersey is reported, thus extending previous research of municipalities at more refined levels of analysis. Alcohol outlet densities were significant predictors in regression models, but rates of violent crime were better predicted in larger units (R2 = .673 for the census tract level vs. .543 at the census block group level). Alcohol outlet densities, however, were more predictive of violent crime at smaller units of analysis (change in R2 with the addition of alcohol outlet densities was .194 at the census tract level vs. .278 at the census block group level). Findings suggest that alcohol outlets represent a form of "undesirable land use" in urban neighborhoods that are a manifestation of increasingly concentrated economic disadvantage in the United States.

The sale of alcoholic beverages to minors.

This study reports the findings of a field trial designed to assess the extent of alcohol sales to minors in one county in northwest New Jersey. Two 19-year-old males were successful in purchasing alcoholic beverages in 27 of 46 (58.7 percent) establishments visited. On the following day, 23 of the establishments that sold the alcohol were visited again and, on this occasion, 18 (78.3 percent) sold alcohol to the minor. This study supports the findings from surveys that show that underage drinkers can obtain alcohol with ease. Many community groups are now taking action to rectify this situation, and data of the type reported in this paper can be used to assess the effectiveness of their actions.

The use of the Severity of Alcohol Dependence Questionnaire (SADQ) on a sample of problem drinkers presenting at a district general hospital.

Severity of alcohol dependence and patients' consistency of responses to the Severity of Alcohol Dependence Questionnaire (SADQ) were investigated in a sample of 127 problem drinkers, presenting to either medical or psychiatric services of a district general hospital. Nearly 2/3 of the sample were found to be mild to moderate drinkers. Intercorrelations of the sections of the questionnaire were highly significant for the total sample. However, in mildly dependent drinkers, consistency between sections was less marked. Implications for treatment and research are discussed.

The perception of problem drinkers by general hospital staff, general practitioners and alcoholic patients.

A sample of 275 subjects (general hospital staff, general practitioners and alcoholic patients) was investigated regarding their perception of problem-drinkers. A set of semantic differential scales was used, and subjects were asked to evaluate the concepts of "problem drinker," "self" and "ideal self." Psychological distance was measured in terms of bipolar personality constructs between each of the above concepts. Significant differences were found between the groups in terms of concept evaluation and psychological distance. The implications of these findings for both research and treatment are discussed.

Spatial dynamics of alcohol availability, neighborhood structure and violent crime.

OBJECTIVE: This study examined the relationship between neighborhood social structure, alcohol outlet densities and violent crime in Camden, New Jersey. METHOD: Data pertaining to neighborhood social structure, violent crime and alcohol density were collected for 98 block groups, and analyzed using bivariate, multivariate and spatial analyses. RESULTS: Each type of analysis showed that those areas with high alcohol outlet densities experienced more violent crime than low-density areas, after controlling for neighborhood social structure. In the multivariate regression analysis, alcohol outlet densities explained close to one fifth of the variability in violent crime rates across block groups--more than any one of the neighborhood structural variables included in the analysis. These findings were replicated in the spatial analysis, which also showed that alcohol outlet densities contributed significantly to violent crime within target block groups but not in adjacent block groups. CONCLUSIONS: High alcohol outlet density is associated with high rates of violent crime in this urban community. Spatial analysis suggests that alcohol outlets elevate the rate of violent crime within the immediate neighborhood context, not in surrounding neighborhoods.

Co-morbidity and treatment needs among nursing home residents receiving alcohol and drug treatment.

This study profiles nursing home residents receiving alcohol and drug treatment, describing their sociodemographic, health, and treatment characteristics. We analyzed 3,662 admission assessments in the Minimum Data Set for people receiving alcohol/drug treatment from June, 1998 through September, 2000. These residents were likely to be male and under age 50. More than half were White and 29 percent were African American. Typically, these residents were not physically or cognitively impaired. However, more than 39 percent had unstable health patterns and almost 21 percent had HIV disease. Thirty-eight percent had a history of mental health conditions, with 24 percent having depression and almost 18 percent having schizophrenia. At least 75 percent received no psychological therapy in the previous 7 days and a majority did not receive antipsychotic, antianxiety, or antidepressant medications. These analyses indicate that most recently admitted residents receiving alcohol/drug treatment did not receive mental health therapy in nursing homes.

Distinguishing primary and secondary disorders in studies of alcohol dependence and depression.

This paper is concerned with the relationship between alcohol dependence and depression, and more specifically with the issue of which criteria should be used in distinguishing primary and secondary disorders. The data presented indicate that borderline or subclinical depression frequently precedes the onset of alcohol dependence. This finding is discussed in terms of previous studies, which show that depression is generally secondary to alcohol dependence. Such studies have focused almost exclusively on severe forms of depressive disorder, and, it is argued, used inappropriate criteria to designate the onset of alcohol dependence (e.g. withdrawal phenomena and alcohol-related problems). In contrast to previous studies, the present paper indicates that subclinical episodes of depression should be assessed by clinicians as possible predisposing factors in the development of alcohol dependence. In addition, it is argued that research designed to establish whether alcohol dependence is a primary or secondary disorder when it occurs in the presence of an accompanying psychiatric disorder should measure onset in terms of changes in behaviour such as giving-up existing interests in order to spend time drinking and consuming more alcohol than former companions.