Acute effects of acamprosate and MPEP on ethanol Drinking-in-the-Dark in male C57BL/6J mice.

BACKGROUND: Recently, a simple procedure in mice, Drinking-in-the-Dark (DID), was hypothesized to have value for medication development for human alcoholism. In DID, mice are offered intermittent, limited access to ethanol over a series of days during the dark phase that results in rapid drinking to intoxication in predisposed genotypes. METHODS: We measured the effects of acamprosate or MPEP, metabotropic glutamate 5 receptor (mGluR5) antagonist, on intake of 20% ethanol, plain tap water or 10% sugar water using the DID procedure in male C57BL/6J mice. RESULTS: Acamprosate (100, 200, 300, or 400 mg/kg) dose dependently decreased ethanol drinking with 300 mg/kg reducing ethanol intake by approximately 20% without affecting intake of plain water or 10% sugar water. MPEP (1, 3, 5, 10, 20, or 40 mg/kg) was more potent than acamprosate with 20 mg/kg reducing ethanol intake by approximately 20% and for longer duration without affecting intake of plain water or 10% sugar water. CONCLUSIONS: These results support the hypothesis that mGluR5 signaling plays a role in excessive ethanol intake in DID and suggest DID may have value for screening novel compounds that reduce overactive glutamate signaling for potential pharmaceutical treatment of excessive ethanol drinking behavior.

Menopause symptoms in HIV-infected and drug-using women.

OBJECTIVE: To examine the association of HIV infection, drug use, and psychosocial stressors with type and frequency of menopause symptoms. DESIGN: In a cross-sectional study, HIV-infected and HIV-uninfected midlife women underwent standardized interviews on menopause status and symptoms, demographic characteristics, depressive symptoms, negative life events, and substance abuse. Body mass index (BMI), HIV serostatus, and CD4 count were measured. Associations between study variables and menopause symptoms were assessed using generalized estimating equations. RESULTS: Of 536 women not on hormone therapy, 48% were black, 42% were Hispanic, 54% were HIV positive, and 30% recently had used illicit drugs. The mean age was 45 +/- 5 years; 48% of the women were identified as premenopausal, and 37% were perimenopausal. Psychological symptoms were most prevalent (89%), followed by arthralgias (63%) and vasomotor symptoms (61%). Perimenopausal women reported significantly more menopause symptoms than premenopausal women (ORadj 1.34, 95% CI, 1.09-1.65). HIV-infected women were more likely to report menopause symptoms than uninfected women (ORadj 1.24, 95% CI, 1.02-1.51). Among HIV-infected women not on highly active antiretroviral therapy, symptoms decreased as the CD4 count declined. Increased menopause symptoms were significantly associated with depressive symptoms (ie, Center for Epidemiologic Studies Depression scale score > 23, ORadj1.82, 95% CI, 1.46-2.28), and with experiencing more than three negative life events (ORadj 2.08, 95% CI, 1.54-2.81). Increasing BMI (per kg/m) was also associated with more menopause symptoms (ORadj 1.03, 95% CI, 1.02-1.05). CONCLUSION: HIV-infected women reported more menopause symptoms than HIV-uninfected women, but symptoms were less frequent in women with more advanced HIV disease. Depressive symptoms and negative life events were also highly associated with symptoms. Further study of menopause symptoms and HIV-related factors is warranted. Mental health interventions may also have a role in ameliorating menopause symptoms.

Associations between posttraumatic stress disorder and hemoglobin A1(C) in low-income minority patients with diabetes.

OBJECTIVE: Posttraumatic Stress Disorder (PTSD) is prevalent among low-income minorities and is associated with poorer health. However, the association between PTSD and hemoglobin A1(C) (A1(C)) among patients with diabetes has not been fully described. The objective of this cross-sectional study was to evaluate associations between PTSD and A1(C) among low-income minorities with diabetes. METHOD: Adults with diabetes were recruited from a network of primary care clinics. Data were obtained from surveys and electronic medical records. Lifetime PTSD symptoms were assessed using the Structured Clinical Interview-DSM-IV and depressive symptoms with the Patient Health Questionnaire-9. A1(C) was obtained from chart review. RESULTS: Of 103 adults analyzed, 12% had lifetime full PTSD and 12% had subthreshold PTSD. On backward stepwise logistic regression, patients with any PTSD symptoms were significantly more likely to have an A1(C) >7% compared to patients without symptoms (OR(adj) 2.98, 95% CI 1.04-8.52, P=.04). An A1(C) >7% also was associated with an interaction between PTSD symptoms and longer diabetes duration (P<.05). CONCLUSION: In this cohort of low-income minorities with diabetes, lifetime PTSD symptoms were significantly associated with an A1(C) >7%.

Evaluation of synergistic antioxidant potential of complex mixtures using oxygen radical absorbance capacity (ORAC) and electron paramagnetic resonance (EPR).

Previous research has demonstrated that certain combinations of compounds result in a decrease in toxic or pro-oxidative effects, previously noted when compounds were administered singly. Thus, there is a need to study many complex interactions further. Two in vitro techniques [electron paramagnetic resonance (EPR) and oxygen radical absorbance capacity (ORAC) assays] were used in this study to assess pro- and antioxidant capacity and synergistic potential of various compounds. Rutin, p-coumaric acid, abscisic acid, ascorbic acid, and a sugar solution were evaluated individually at various concentrations and in all 26 possible combinations at concentrations found in certain foods (honey or papaya), both before and after simulated digestion. EPR results indicated sugar-containing combinations provided significantly higher antioxidant capacity; those combinations containing sugars and ascorbic acid demonstrated synergistic potential. The ORAC assay suggested additive effects, with some combinations having synergistic potential, although fewer combinations were significantly synergistic after digestion. Finally, ascorbic acid, caffeic acid, quercetin, and urate were evaluated at serum-achievable levels. EPR analysis did not demonstrate additive or synergistic potential, although ORAC analysis did, principally in combinations containing ascorbic acid.