Alteration of voluntary ethanol and saccharin consumption by the neurosteroid allopregnanolone in mice

RATIONALE: The neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone, ALLOP) is a positive modulator of gamma-aminobutyric acid type A (GABA(A)) receptors. Recent findings indicate that ethanol (EtOH) and ALLOP share common mechanisms of action and that ALLOP may modulate some of EtOH's abuse-related effects. OBJECTIVES: The present studies investigated whether ALLOP pretreatment altered voluntary EtOH consumption in male and female C57BL/6J mice, and voluntary saccharin and quinine consumption in male C57BL/6J mice. METHODS: Mice had access to two drinking tubes containing water versus 5% or 10% (v/v) EtOH or a tastant for 2 h each day at the beginning of the dark cycle. Following establishment of stable consumption, animals received 2 days of vehicle followed by 3 days of ALLOP injections (0, 3.2, 10, or 17 mg/kg, IP), immediately prior to EtOH or tastant access. RESULTS: Prior to injection, the 2-h baseline dose of the 10% EtOH solution consumed was 1.31 g/kg (expt 1) or 2.46 g/kg (expt 3) for male and 2.21 g/kg (expt 2) for female mice. Baseline intake of the 5% EtOH solution was 0.60 g/kg for males and 0.75 g/kg for females (expt 5). In males, ALLOP administration significantly and dose-dependently increased consumption of both EtOH solutions during the first hour of availability without affecting water intake. In females, ALLOP did not significantly alter EtOH consumption. Lastly, ALLOP significantly increased saccharin, but not quinine, consumption in males (females were not tested). CONCLUSIONS: ALLOP may increase voluntary EtOH consumption in male mice by altering its reinforcing effects. The lack of significant effect on quinine and water consumption suggests that ALLOP does not simply increase consumption of all fluids.     

Establishing the feasibility of performance measures for alcohol and other drugs

The Washington Circle (a multiple-disciplinary group of providers, researchers, managed care representatives, and public policy representatives) examined three performance measures for alcohol and other drug (AOD) services. These measures, which were developed and applied to managed care organizations' administrative data for their commercial enrollees, are: (a) identification, the percent of adult enrollees with AOD diagnoses; (b) initiation, the percent of adults with an inpatient AOD admission or with an index outpatient visit for AOD abuse or dependence and any additional AOD services within 14 days of identification; and (c) engagement, the percent of adults diagnosed with AOD disorders that receives two additional AOD services within 30 days of the initiation of care. We conclude that using administrative databases to compare managed care organizations' performance is feasible, meaningful and informative. The article discusses issues in interpreting performance measures in several areas: organizational structure of alcohol and other drug services, information available for measurement, and computational issues.     

Psychopathology influences treatment retention among drug-dependent women

Three subgroups of drug dependent women (N = 78) were identified through cluster analysis on MCMI-II scores. Group 1 (26%) presented a relatively benign clinical picture. In contrast, Group 2 (37%) evidenced severe addiction, psychiatric (Axis I), and personality (Axis II) problems. Group 3 (37%) was characterized by fewer Axis I problems, prominent addiction and externalizing (Cluster B) personality deficits. Group membership was significantly associated with retention in a gender-specific day treatment program. Group 2 experienced rapid attrition, with only 36% completing treatment, compared to 57% for Group 1 and 76% for Group 3. Results indicate that drug-dependent women with externalizing psychopathology can be retained in treatment when environmental barriers are removed and an adequate “holding environment” is maintained. However, women with severe psychiatric problems, unstable mood, and interpersonal deficits are less likely to complete treatment. Early identification of women at risk for drop-out affords an opportunity to intervene to prevent its occurrence.     

Nutrition and the early origins of adult disease

There is now overwhelming evidence that much of our predisposition to adult illness is determined by the time of birth. These diseases appear to result from interactions between our genes, our intrauterine environment and our postnatal lifestyle. Those at greatest risk are individuals in communities making a rapid transition from lives of 'thrift' to a lives of 'plenty'. From a global perspective, such origins of diabetes, coronary heart disease and stroke, should render research in these fields as one of the highest priorities in human health care. Prevention will be enhanced by elucidation of the mechanisms by which the fetus is programmed by the mother for the life she expects it to live. At the present time, there is evidence that fetal nutrition and premature exposure to cortisol are effective intrauterine triggers, but a multitude of alternative pathways require investigation. It is also likely that programming extends across generations, and may involve the embryo and perhaps the oocyte. An oocyte that becomes an adult human develops in the uterus of its grandmother, so further research is required to describe the role of environments of grandmothers and mothers in predisposing offspring to health or illness in adult life.     

Legal options for achieving public health outcomes.

To achieve desired public health outcomes, state agencies can choose among several legal mechanisms; however, no "best practice" guidelines are available to help them choose the most effective mechanism for a given situation. This article offers such guidance by comparing the relative advantages and disadvantages of laws, regulations, policies, and contracts. Factors compared include flexibility, the need for legislative involvement, the nature of the rulemaking process, enforceability, ability to reach target populations, and generalizability. Contracts, in particular, are described as an effective but underutilized mechanism for achieving successful public health outcomes.     

Benchmarking HIPAA compliance

One of the nation's largest academic medical centers is benchmarking its operations using internally developed software to improve privacy/confidentiality of protected health information (PHI) and to enhance data security to comply with HIPAA regulations. It is also coordinating the development of a web-based interactive product that can help hospitals, physician practices, and managed care organizations measure their compliance with HIPAA regulations.     

Usual dietary isoflavone intake, bone mineral density, and bone metabolism in postmenopausal women

Clinical trials of isoflavone supplementation and bone density have been of relatively short duration and yielded inconsistent results. Few studies examined the effects of usual dietary isoflavone intake on bone density, and none examined the effects on markers of bone turnover. This cross-sectional study examines the association of usual, unsupplemented dietary soy intake with bone density at the lumbar spine and hip and markers of bone turnover in postmenopausal women. Participants were 208 postmenopausal Southern California women aged 45-74 years. Information on behavioral and lifestyle factors was obtained, and dietary intake of isoflavones over the past year was assessed with a standardized questionnaire. Bone density was measured at the spine and hip with dual energy x-ray absorptiometry (DEXA). Urinary type I collagen cross-linked N-telopeptides (N-Tx) and pyridinium cross-links (PYR), both markers of bone resorption, and bone alkaline phosphatase (BAP), a marker of bone formation, were assayed. After adjustment for age and obesity, women with the highest daily intake of dietary genistein had N-Tx concentrations 18% lower than those of women who reported no daily genistein consumption (mean 37.29 vs. 45.44, respectively, p = 0.01). After adjustment for all covariates, there were trends toward significant differences in N-Tx (p = 0.09) and spine bone density (p = 0.07), whereby women with the highest level of isoflavone consumption had greater bone density at the spine. These results suggest that usual, unsupplemented dietary isoflavone consumption may be protective against bone loss in postmenopausal women through a reduction in bone resorption.