Differential effects of ethanol on plasma catecholamine levels in rats

Acute ethanol administration (1-4 g/kg, i.p.) had no effect on plasma catecholamine levels in nonstressed animals except at the highest dose where levels of both catecholamines increased. In animals stressed for 30 min, the higher doses had a biphasic effect on plasma catecholamines; at earlier times during stress a reduction in stress-induced increases in both catecholamines was seen, whereas later during stress or after release from stress an increase was noted. Semi-chronic ethanol administration (0.5 and 2 g/kg/day, i.p.) had no significant effect on plasma catecholamine levels in nonstressed rats. In stressed rats, ethanol reduced stress-induced catecholamine increases but these reductions were less than those seen after acute administration. Although ethanol reduced the gross behavioral stress response, no correlation between gross behavioral and biochemical responses was detected. These data show that ethanol can indeed reduce the behavioral and biochemical stress responses in rats but that effects seen depend on the state (nonstressed vs stressed) of the animal, the dose of ethanol (low vs high) used, the length of ethanol administration (acute vs semi-chronic), and the time of measurement of the catecholamine level after ethanol administration.     

恩替卡韦与拉米夫定治疗HBeAg阴性慢性乙型肝炎的对照研究

Ⅱ期临床试验已经证实恩替卡韦是一种治疗HBeAg阴性慢性乙型肝炎有效和可选择的抗病毒药物。采用双盲法将648例未曾接受过核苷类药物治疗的HBeAg阴性慢性乙型肝炎随机分配进入恩替卡韦（0．5mg／d）治疗组或拉米夫定（100mg／d）治疗组，疗程至少52wk。     

Effects of Lead Acetate on Learning and Memory in Rats

Under the conditions employed lead acetate in toxic quantities had no significant effects on learning or memory in rats.     

The Effect of 12-Step-Based Fellowship Participation on Abstinence Among Dually Diagnosed Persons: A Two-Year Longitudinal Study

Abstract

A large percentage of individuals are dually-diagnosed with a psychiatric disorder and a substance use disorder. Such persons typically face more difficulties and have poorer outcomes than do single disorder substance users. Among noncomorbid substance users, treatment and participation in 12-Step groups have been shown to enhance the likelihood of abstinence from substance misuse. Specialized 12-Step based fellowships have recently emerged to address the recovery needs of dually-diagnosed persons. The present study is a longitudinal investigation of the effect of such 12-Step based groups on abstinence among dually-diagnosed persons. Participants were members of Double Trouble in Recovery (DTR) who were recruited at community-based meetings in New York City and reinterviewed twice at yearly intervals. Generalized estimating equation analysis indicated that, over the two-year study period, ongoing DTR attendance was significantly associated with a greater likelihood of abstinence after controlling for other pertinent variables, such as mental health symptoms. For clinicians, these findings underline the importance of fostering stable affiliation with specialized 12-Step based groups among their clients.     

Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab

Background Post hoc analyses assessed the prognostic and predictive value of baseline alpha-fetoprotein (AFP), as well as clinical outcomes by AFP response or progression, during treatment in two placebo-controlled trials (REACH, REACH-2).Methods Serum AFP was measured at baseline and every three cycles. The prognostic and predictive value of baseline AFP was assessed by Cox regression models and Subpopulation Treatment Effect Pattern Plot method. Associations between AFP (≥ 20% increase) and radiographic progression and efficacy were assessed.Results Baseline AFP was confirmed as a continuous (REACH, REACH-2; p < 0.0001) and dichotomous (≥400 vs. <400 ng/ml; REACH, p < 0.01) prognostic factor, and was predictive for ramucirumab survival benefit in REACH (p = 0.0042 continuous; p < 0.0001 dichotomous). Time to AFP (hazard ratio [HR] 0.513; p < 0.0001) and radiographic (HR 0.549; p < 0.0001) progression favoured ramucirumab. Association between AFP and radiographic progression was shown for up to 6 (odds ratio [OR] 5.1; p < 0.0001) and 6–12 weeks (OR 1.8; p = 0.0065). AFP response was higher with ramucirumab vs. placebo (p < 0.0001). Survival was longer in patients with an AFP response than patients without (13.6 vs. 5.6 months, HR 0.451; 95% confidence interval, 0.354–0.574; p < 0.0001).Conclusions AFP is an important prognostic factor and a predictive biomarker for ramucirumab survival benefit. AFP ≥ 400 ng/ml is an appropriate selection criterion for ramucirumab.Clinical Trial Registration ClinicalTrials.gov, REACH ({"type":"clinical-trial","attrs":{"text":"NCT01140347","term_id":"NCT01140347"}}NCT01140347) and REACH-2 ({"type":"clinical-trial","attrs":{"text":"NCT02435433","term_id":"NCT02435433"}}NCT02435433).Subject terms: Oncology, Biomarkers     

Postmenopausal bone loss at multiple skeletal sites: relationship to estrogen use

Bone mineral content (BMC) was measured in the distal radius, proximal radius, and os calcis in 608 postmenopausal women, and the values were compared to vertebral osteoporosis and compression fractures determined radiographically, as well as to history of estrogen use. Current estrogen users had significantly higher BMC at all appendicular sites as compared to non-users. Prior estrogen users had lower appendicular BMC's than current users, but they were still significantly higher than non-users. However, radiographic assessment of the lumbar spine showed no difference in osteoporosis or compression fracture prevalence between prior users and non-users of estrogen, whereas current estrogen users had a significantly lower prevalence of osteoporosis in the spine. These findings suggest that estrogen effect on trabecular bone in the os calcis may be more transient than on cortical, appendicular bone. They also suggest that long term or permanent estrogen replacement is required to prevent spinal compression fractures.     

The Role of Serotonin (5-HT) in Behavioral Control: Findings from Animal Research and Clinical Implications

The neurotransmitters serotonin and dopamine both have a critical role in the underlying neurobiology of different behaviors. With focus on the interplay between dopamine and serotonin, it has been proposed that dopamine biases behavior towards habitual responding, and with serotonin offsetting this phenomenon and directing the balance toward more flexible, goal-directed responding. The present focus paper stands in close relationship to the publication by Worbe et al. (2015), which deals with the effects of acute tryptophan depletion, a neurodietary physiological method to decrease central nervous serotonin synthesis in humans for a short period of time, on the balance between hypothetical goal-directed and habitual systems. In that research, acute tryptophan depletion challenge administration and a following short-term reduction in central nervous serotonin synthesis were associated with a shift of behavioral performance towards habitual responding, providing further evidence that central nervous serotonin function modulates the balance between goal-directed and stimulus-response habitual systems of behavioral control. In the present focus paper, we discuss the findings by Worbe and colleagues in light of animal experiments as well as clinical implications and discuss potential future avenues for related research.