CE-108, a new macrolide tetraene antibiotic

In the search for strains producing antifungal compounds, a new tetraene macrolide CE-108 (3) has been isolated from culture broth of Streptomyces diastaticus 108. In addition, the strain also produces the previously described tetraene rimocidin (1) and also the aromatic polyketide oxytetracycline. Both tetraene compounds, structurally related, are produced in a ratio between 25 to 35% (CE-108 compared to rimocidin), although it can be inverted toward CE-108 production by changing the composition of the fermentation medium. This paper deals with the characterization of the producer strain, fermentation, purification, structure determination and biological properties of the new macrolide tetraene CE-108.     

Small molecule activators of the heat shock response and neuroprotection from stroke

Various cellular defense pathways are mobilized in response to stress that serve to limit potential damage to organelles and biochemical pathways that would disrupt normal cellular function or trigger cell death. Strategies utilized by cells subjected to various forms of stress include the activation of detoxification systems that act to eliminate the primary damaging molecules, remove damaged cellular macromolecules, or restore organelle and macromolecule function in cases where loss of activity is generated by reversible modifications or alterations in conformation (ie, misfolding). Central to many intracellular defense mechanisms that operate to limit damage to protein function are molecular chaperones of the heat shock protein (HSP) family. This review briefly discusses the molecular mechanisms that are thought to dictate the well-established neuroprotective effects of HSPs and highlight the recent attempts to use pharmacologic approaches to activate this important cellular defense pathway.     

Relevance of neuroscience to effective education for students with reading and other learning disabilities

New directions in educational assessment and instruction are supported by recent advances in the neurosciences. Among these are early identification of potential learning problems through brief, efficient assessments of specific language skills that predict later reading outcomes; early intervention that systematically targets critical linguistic processing skills; and the necessity of stimulating all functions of a reading, writing, or computing brain.     

Sociodemographic disparities in supplemental service utilization among male methadone patients

The high prevalence of health and psychosocial needs among methadone treatment patients has prompted efforts to supplement methadone treatment with additional services. Research has generally focused on linking supplemental service utilization to drug treatment outcomes, with fewer studies aimed at understanding supplemental service utilization itself. This study with randomly selected male methadone maintenance treatment program (MMTP) patients examined associations between sociodemographic factors and supplemental service utilization while controlling for need for services and treatment duration. Findings indicate that MMTP patients who are African American, Latino, uninsured, or have less education were less likely to report any supplemental service utilization. Hypotheses positing sociodemographic differences in regular vs. occasional service utilization were not supported. There is a need to improve access to supplemental services for minority and disadvantaged MMTP patients, and MMTPs may represent an important venue to address health disparities in general.     

Cannabis use and psychotic disorders: an update

This paper evaluates three hypotheses about the relationship between cannabis use and psychosis in the light of recent evidence from prospective epidemiological studies. These are that: (1) cannabis use causes a psychotic disorder that would not have occurred in the absence of cannabis use; (2) that cannabis use may precipitate schizophrenia or exacerbate its symptoms; and (3) that cannabis use may exacerbate the symptoms of psychosis. There is limited support for the first hypothesis. As a consequence of recent prospective studies, there is now stronger support for the second hypothesis. Four recent prospective studies in three countries have found relationships between the frequency with which cannabis had been used and the risk of receiving a diagnosis of schizophrenia or of reporting psychotic symptoms. These relationships are stronger in people with a history of psychotic symptoms and they have persisted after adjustment for potentially confounding variables. The absence of any change in the incidence of schizophrenia during the three decades in which cannabis use in Australia has increased makes it unlikely that cannabis use can produce psychoses that would not have occurred in its absence. It seems more likely that cannabis use can precipitate schizophrenia in vulnerable individuals. There is also reasonable evidence for the third hypothesis that cannabis use exacerbates psychosis. [Hall W, Degenhardt L, Teeson M. Cannabis use and psychotic disorders: an update. Drug Alcohol Rev 2004;23:433-443]     

Changes in patterns of drug use among injecting drug users following changes in the availability of heroin in New South Wales, Australia

The aim of this study was to examine changes in drug use patterns among groups of injecting drug users (IDU) who remained in the drug market during a period of reduced heroin availability in NSW, Australia. Cross-sectional data collected from regular IDU interviewed as part of the NSW Illicit Drug Reporting System (IDRS) between 1996 - 2003 were analysed. Drug use patterns, reported drug availability and price were assessed. There was a marked decrease in the frequency of heroin use during the period of reduced availability in 2001, with some increase in 2002 and 2003. Heroin availability and frequency of use have not returned to levels reported prior to 2001; however; even at the peak of the reduction in supply, users continued to access heroin. There was a significant shift among IDU from heroin to cocaine during 2001, which subsequently reversed. The availability of cocaine has fluctuated in recent years, but the price has remained stable. The price of heroin appeared to be more responsive to market fluctuations, and co-varied with heroin availability. IDU used cocaine when heroin was less available; however, patterns of cocaine use were not maintained. The frequency of heroin use remained lower, which may be indicative of a less consistent supply, increased price or increased numbers of IDU entering treatment. The reduced supply of heroin in 2001 highlighted the adaptable nature of IDU patterns of use, indicative of the need for a commensurate treatment response. It also highlighted the importance of the ongoing monitoring of drug trends in Australia. [Roxburgh A, Degenhardt L, Breen C. Changes in patterns of drug use among injecting drug users following changes in the availability of heroin in New South Wales, Australia. Drug Alcohol Rev 2004;23:287-294]     

Immunoreactive ghrelin in human cord blood: relation to anthropometry,leptin, and growth hormone

BACKGROUND: Ghrelin is secreted by the stomach, the hypothalamus, and the placenta in humans and has growth hormone-secreting and orexigenic properties. Leptin is secreted mainly by the adipocyte, plays a major role in energy balance, and reflects fat mass in infants as well as adults. Leptin and ghrelin central effects are mediated, at least partly, through the neuropeptide Y/Y1 receptor pathway in the hypothalamus. METHODS: We determined whether ghrelin is also present in the fetus and investigated its relationship to leptin, growth hormone, birth weight, and calf and abdominal circumferences in 90 full-term neonates. RESULTS: Immunoreactive ghrelin was detected in all cord samples (mean +/- SD, 187 +/- 88 pmol/L; range, 66-594 pmol/L). In contrast to leptin, ghrelin concentrations of boys and girls were not statistically different. In female neonates, ghrelin is inversely correlated with anthropometric measures. In male neonates, ghrelin is positively correlated with leptin and negatively with growth hormone. CONCLUSION: The presence of significant ghrelin concentrations in all neonates before the first feeding is intriguing. Unlike the fairly constant concentrations and effects of leptin over the short term, the wide variability of ghrelin concentrations observed in newborns raises the possibility that ghrelin secretion causes short-term changes in feeding behavior. We suggest that ghrelin may play a physiologic role in the initiation of feeding.