Personal goals as predictors of college student drinking motives,alcohol use and related problems

OBJECTIVE: Although there has been extensive research examining drinking motives, relatively little of that research has focused on those factors that might underlie drinking motives. The present study examines whether nonalcohol-related motives (personal goals) can predict drinking motives, self-reported drinking and alcohol-related problems in a college student sample. METHOD: For an experiment on "attitudes and drinking," 290 volunteer undergraduate students (169 women and 121 men) completed measures of daily goal functioning (Personal Projects Analysis), drinking motives (Drinking Motives Questionnaire), frequency and quantity of alcohol consumed and alcohol-related problems (Drinkers Inventory of Consequences). RESULTS: Using path analysis, it was found that nonalcohol-related goals serve as significant distal predictors of alcohol-related problems, with their effects almost entirely mediated by drinking motives and/or drinking level. Perceptions of life goals involving goal self-efficacy, meaningfulness and social support appear to be significant protective factors, and goal-related distress is a significant risk factor. CONCLUSIONS: The present study extends previous research by focusing on a more idiographic, personally meaningful manifestation of motivation through the evaluation of nonalcohol-related personal goals. The daily pursuits of college students were shown to be predictive of drinking and drinking-related problems, especially as mediated through drinking motives. The findings suggest that several goal mechanisms could be considered for their potential role in improving interventions.     

Evidence that intermittent,excessive sugar intake causes endogenous opioid dependence

OBJECTIVE: The goal was to determine whether withdrawal from sugar can cause signs of opioid dependence. Because palatable food stimulates neural systems that are implicated in drug addiction, it was hypothesized that intermittent, excessive sugar intake might create dependency, as indicated by withdrawal signs. RESEARCH METHODS AND PROCEDURES: Male rats were food-deprived for 12 hours daily, including 4 hours in the early dark, and then offered highly palatable 25% glucose in addition to chow for the next 12 hours. Withdrawal was induced by naloxone or food deprivation. Withdrawal signs were measured by observation, ultrasonic recordings, elevated plus maze tests, and in vivo microdialysis. RESULTS: Naloxone (20 mg/kg intraperitoneally) caused somatic signs, such as teeth chattering, forepaw tremor, and head shakes. Food deprivation for 24 hours caused spontaneous withdrawal signs, such as teeth chattering. Naloxone (3 mg/kg subcutaneously) caused reduced time on the exposed arm of an elevated plus maze, where again significant teeth chattering was recorded. The plus maze anxiety effect was replicated with four control groups for comparison. Accumbens microdialysis revealed that naloxone (10 and 20 mg/kg intraperitoneally) decreased extracellular dopamine (DA), while dose-dependently increasing acetylcholine (ACh). The naloxone-induced DA/ACh imbalance was replicated with 10% sucrose and 3 mg/kg naloxone subcutaneously. DISCUSSION: Repeated, excessive intake of sugar created a state in which an opioid antagonist caused behavioral and neurochemical signs of opioid withdrawal. The indices of anxiety and DA/ACh imbalance were qualitatively similar to withdrawal from morphine or nicotine, suggesting that the rats had become sugar-dependent.     

Anti-HIV agents derived from the ent-kaurane diterpenoid linearol

Twenty-six semisynthetic ent-kaurane derivatives of linearol (1) have been investigated for their anti-HIV effects. Five compounds (4, 7, 11, 25, and 26) showed significant activity against HIV replication in H9 lymphocyte cells with EC(50) values in the range <0.1-3.11 microg/mL. With TI values of 163 and 184, compounds 4 and 25 are especially promising for further development as potential anti-HIV agents.     

Primary care: the next renaissance

Three decades ago, a renaissance helped create the foundations of primary care as we know it today. In recent years, however, new challenges have confronted primary care. We believe that the current challenges can be overcome and may, in fact, present an opportunity for a new renaissance of primary care to address the needs of our population. In this paper, we suggest seven core principles and a set of actions that will support a renaissance in, and a positive future for, primary care. The seven principles are 1) Health care must be organized to serve the needs of patients; 2) the goal of primary care systems should be the delivery of the highest-quality care as documented by measurable outcomes; 3) information and information systems are the backbone of the primary care process; 4) current health care systems must be reconstructed; 5) the health care financing system must support excellent primary care practice; 6) primary care education must be revitalized, with an emphasis on new delivery models and training in sites that deliver excellent primary care; and 7) the value of primary care practice must be continually improved, documented, and communicated. At the start of the 21st century, a vital, patient-centered primary care system has much to offer a rapidly changing population with increasingly diverse needs and expectations. If we keep the needs of persons and patients clearly in sight and design systems to meet those needs, primary care will thrive and our patients will be well served.     

Hydrolytically activated etoposide prodrugs inhibit MDR-1 function and eradicate established MDR-1 multidrug-resistant T-cell leukemia

Effective therapy of high-risk leukemia with established cytotoxic drugs may be limited by poor antitumor efficacy, systemic toxicity, and the induction of drug resistance. Here, we provide the first evidence that hydrolytically activated prodrugs may overcome these problems. For this purpose, VP16 was functionally blocked by hydrolytically cleavable carbonate linkers with unique characteristics to generate 2 novel prodrugs of VP16. First, we established a more than 3-log higher efficacy of the 2 prodrugs compared with VP16 on a panel of naturally drug-resistant tumor cell lines. Second, the prodrugs did overcome VP16-induced multidrug resistance-1 gene (MDR-1)-mediated multidrug resistance in vitro in a newly established VP16-resistant T-cell leukemia cell line MOVP-3 by functionally blocking MDR-1-mediated efflux. Third, in vivo studies showed a maximum tolerated dose of ProVP16-II (> 45mg/kg), which was at least 3-fold higher than that of VP16 (15 mg/kg). Finally, tests of ProVP16-II in a multidrug-resistant xenograft model of T-cell leukemia expressing MDR-1 indicated that only the mice treated with this prodrug revealed a complete and long-lasting regression of established, drug-resistant leukemia. In summary, the hydrolytically activated etoposide prodrugs proved effective against multidrug-resistant T-cell leukemia in vitro and in vivo and provide proof of concept for a highly promising new strategy for the treatment of MDR-1 drug-resistant malignancies.     

Polymorphism of the codon 129 of the prion protein (PrP) gene and neuropathology of cerebral ageing

We studied whether codon 129 polymorphism of the PrP gene modulates the presence of tau- and Abeta-associated lesions among 188 patients over 70 years of age without evidence of dementia. Val allele carriers, either heterozygotes or homozygotes, were more frequently affected by Abeta-associated lesions than non Val allele carriers, whereas there were no differences for tau-positive neurones. Val allele carriers also had more focal and diffuse Abeta deposits. This association was most significant in the highest Braak's stages for neurofibrillary tangles (>/=III). In this group, cases with at least one Val allele had nearly twice as many Abeta-associated lesions. The most affected areas were the entorhinal cortex, TF-TH and the superior temporal cortex, where odds ratios for focal Abeta deposits ranged from 3.5 to 4.6.