GABAergic Transmission in the Nucleus Accumbens Is Involved in the Termination of Ethanol Self-Administration in Rats

Long-Evans rats ( n = 12) were trained to lever-press on a fixed-ratio 4 schedule of reinforcement with ethanol (10% v/v) presented as the reinforcer. After implantation of bilateral stainless-steel guide cannulae aimed at the nucleus accumbens, site-specific microinjections of muscimol (1–30 ng) and bicuculline (1–10 ng) were tested for effects on ethanol-reinforced responding. Baseline response patterns were characterized by initial high rates that terminated abruptly after ∼20 min. Muscimol administration in the nucleus accumbens decreased the total number of ethanol-reinforced responses and obtained reinforcers. Bicuculline also decreased ethanol-reinforced responses and reinforcers at the highest dose tested. When a dose of bicuculline (1 ng) that was ineffective by itself was coadministered with an effective dose of muscimol (10 ng), the muscimol-induced decreases in responding were blocked. Analysis of response patterns showed that muscimol decreased ethanol self-administration by terminating responding, normally lasting 20 min, after ∼10 min with no changes in local response rate. Bicuculline decreased total responding by producing parallel, but nonsignificant, changes in time course and response rate. These data suggest that GABAergic transmission in the nucleus accumbens is involved in the termination, but not the onset or maintenance of ethanol self-administration. The specificity of this effect gives emphasis to the importance of measuring behavioral parameters, as well as products of behavior (such as intake volume) in the study of ethanol self-administration.     

Failure of a schedule-induction procedure to increase ethanol intake in an established limited-access self-administration condition.

Determining mechanisms that can increase ethanol consumption during a single drinking bout is central to understanding alcohol abuse. When rodents are used as models to study excessive drinking, most often limited and transient increases in bout size are found with various manipulations. In a variety of studies, investigators have reported that schedule-induced drinking can result in excessive consumption of either water or alcohol (ethanol) during a single drinking period in food-restricted rats. The question examined in this experiment was, Could a schedule-induction paradigm increase bout size in nondeprived rats already self-administering ethanol? After the rats were trained to self-administer a 10% (volume/volume) ethanol solution in a fixed daily drinking session, non-response-contingent presentation of a 10% (weight/volume) sucrose solution, on a fixed-time, 120-s schedule, was used to determine whether additional ethanol consumption could be induced. This was followed by the use of a fixed-time, 300-s schedule and then, by using the fixed-time, 120-s schedule, with the presentation of a 2% (weight/volume) sucrose solution. None of these conditions induced an increase in ethanol self-administration. The results indicate that factors that control ethanol bout size in the nondeprived rat are such that the standard schedule-induction condition seems to be ineffective if an ethanol bout has occurred in the recent past.     

Paget's disease of bone in The Netherlands: a population-based radiological and biochemical survey--the Rotterdam Study.

Serum ALP may be a good indicator of Paget's disease in epidemiologic studies. Subjects with raised and normal ALP from a population cohort were matched (1 in 6, total 548), and radiographs were taken. ALP was an excellent marker of the disease (RR, 10.9), but the majority of those affected had normal ALP. INTRODUCTION: Evidence from radiographic surveys of limited skeletal sites has shown that Paget's disease of bone (PDB) is common in the elderly and has a distinct geographic variation. There is no information, however, about the relation of serum alkaline phosphatase (ALP) activity, a marker of the disease, and its prevalence in the population. MATERIALS AND METHODS: We analyzed data from a well-defined Dutch population cohort (the Rotterdam study) with the following specific aims: (1) to assess the relationship between serum ALP activity and prevalence of radiographically diagnosed PDB, (2) to estimate the overall prevalence of the disease in the Netherlands, and (3) to assess the appearance of the disease with time. Using a nested case-control design, subjects with an increased serum ALP and normal serum liver enzymes were matched for gender and age (1 to 6) with subjects with normal serum ALP activity. Radiographs of the thoracic and lumbar spine, pelvis, proximal femurs, knees, wrists, and hands were taken. RESULTS AND CONCLUSIONS: PDB was diagnosed in 20.5% of subjects with elevated serum ALP activity and in 2.3% in those with normal serum ALP activity, increasing with age in both groups. The relative risk (RR) for PDB in the presence of raised serum ALP activity was 10.9 (95% CI, 4.8, 24.9). The estimated prevalence of PDB in the population was 3.6%, and the large majority (about 86%) had normal serum ALP activity, contrasting findings in bone clinics where the opposite is the case. Finally, in subjects with normal and raised serum ALP activity but no PDB at baseline, radiographs taken 6-9 years later showed no evidence of the disease. This study demonstrated that serum ALP activity is a sensitive marker of PDB in men and women >55 years of age, but the majority of those affected have normal serum ALP activity.     

Chylous Ascites Caused by Constrictive Pericarditis

Chylous ascites is an uncommon clinical entity associated with lymphatic obstruction usually caused by underlying malignancy. The authors describe a patient with chylous ascites caused by constrictive pericarditis in the absence of mechanical lymphatic obstruction. Pathophysiological mechanisms for the development of chylous ascites in constrictive pericarditis include augmented lymph production and high impedance to lymph drainage caused by central venous hypertension. After pericardiectomy, the patient's ascites and edema resolved. Constrictive pericarditis should be considered a rare but potentially curable cause of chylous ascites.     

Nursing assessment and nursing diagnosis in patients with peripheral vascular disease

Effective nursing interventions are determined by the nursing diagnoses and associated etiologies. The diagnoses are derived from a complete data base that results from a thorough assessment. As the nurse proceeds through the process of differentiating among diagnoses, the focused cue search is essential. For the client with PVD, lifestyle changes, symptomatology, chronicity of the disease, and frequent contact with the health care system are the major influences on the diagnoses. These clients are likely to have potential for injury, potential for infection, impaired skin integrity, activity intolerance, alteration in tissue perfusion, alteration in comfort, and knowledge deficit. Other diagnoses are probable but are determined by the unique characteristics of each client.     

Microbial infections,immunomodulation, and drugs of abuse

The use of recreational drugs of abuse has generated serious health concerns. There is a long-recognized relationship between addictive drugs and increased levels of infections. Studies of the mechanisms of actions of these drugs became more urgent with the advent of AIDS and its correlation with abused substances. The nature and mechanisms of immunomodulation by marijuana, opiates, cocaine, nicotine, and alcohol are described in this review. Recent studies of the effects of opiates or marijuana on the immune system have demonstrated that they are receptor mediated, occurring both directly via specific receptors on immune cells and indirectly through similar receptors on cells of the nervous system. Findings are also discussed that demonstrate that cocaine and nicotine have similar immunomodulatory effects, which are also apparently receptor mediated. Finally, the nature and mechanisms of immunomodulation by alcohol are described. Although no specific alcohol receptors have been identified, it is widely recognized that alcohol enhances susceptibility to opportunistic microbes. The review covers recent studies of the effects of these drugs on immunity and on increased susceptibility to infectious diseases, including AIDS.