Drugs in salmonid aquaculture--a review

In contrast to mammalian therapeutics, the use of pharmaceutical substances is rather limited in fish. It is basically restricted to anaesthetic agents and anti-infective agents for parasitic and microbial diseases. Anaesthetic agents are used primarily in fish farm and laboratory settings to provide analgesia and immobilization of fish for minor procedures. The anti-infective agents are used for controlling diseases and the choice of drug depends on efficacy, ease of application, human safety, target animal safety including stress to the fish, environmental impact, regulatory approval, costs, and implications for marketing the fish. In this article, the major drugs used in salmonids in North America and Europe will be reviewed and some insight into future directions for drug development and use for the salmonid industry will be introduced. The mechanisms of action, pharmacokinetics, side effects, and uses of the drugs are emphasized.     

N-carbamoyl analogs of Zafirlukast: potent receptor antagonists of leukotriene D4

Exploration of the indole nitrogen region of Zafirlukast (1) has uncovered a potent series of cysteinyl leukotriene D4 (LTD4) antagonists. These studies showed that a variety of functionality could be incorporated in this region of the molecule without sacrificing potency. Efforts to exploit this site in order to improve oral efficacy are discussed.     

An integrative conceptual framework for assessing and treating suicidal behavior in adolescents

Suicidal adolescents represent a uniquely demanding clinical population. Regardless of psychotherapeutic orientation, the existing standards of care demand a relatively broad and integrative approach with multiple and specific treatment targets, as well as ongoing and repeated risk assessment. The current article provides an integrative conceptual framework for these tasks in day to day clinical practice with essentially two goals: (1) to provide a summary of therapeutic and assessment tasks (i.e. the content of therapy and assessment) consistent with existing standards of care and supported by empirical findings, and (2) to emphasize the varied roles, tasks, demands and limitations of psychotherapy with suicidal adolescents.     

Evidence that macrophages are required for T-cell infiltration and rejection of fetal pig pancreas xenografts in nonobese diabetic mice

BACKGROUND: Host macrophages are abundant within fetal pig pancreas xenografts undergoing rejection, but their role is unknown. Therefore, we examined the effect of host macrophage depletion on xenograft rejection. METHODS: Nonobese diabetic (NOD) mice were given clodronate-loaded liposomes intravenously to deplete macrophages. Controls received phosphate-buffered saline (PBS) or PBS-liposomes. General immune status was assessed after 2, 3, and 7 days by (1) fluorescence-activated cell sorter analysis of peripheral blood, spleen, and lymph node cells, (2) immunohistochemistry on spleens, and (3) mixed lymphocyte reaction. Organ-cultured fetal pig pancreas was transplanted under the kidney capsule of NOD mice 3 days after clodronate or PBS injection. Grafts were assessed histologically at 4, 5, 6, and 8 days after transplantation. RESULTS: Splenic macrophages and peripheral blood monocytes were depleted 2 days after clodronate treatment but had recovered within 11 days. T cell, B cell, and dendritic cell numbers were normal in spleen, peripheral blood, and lymph nodes of clodronate-treated mice, and T cells and antigen-presenting cells from these mice functioned normally in mixed lymphocyte reaction. Clodronate treatment markedly reduced graft infiltration by macrophages, T cells, and eosinophils at 4, 5, and 6 days after transplantation, and was associated with maintenance of endocrine cell viability and insulin expression. However, all grafts were rejected 8 days after transplantation, concordant with reappearance of splenic macrophages. CONCLUSIONS: Short-term, specific depletion of macrophages markedly delayed cellular infiltration and rejection of xenografts. The results provide the first evidence that macrophages promote T-cell infiltration and rejection of fetal pig pancreas xenografts in NOD mice.     

Patients and family members: the role of knowledge and attitudes in cancer pain

Cancer pain theoretically comprises sensory, affective, and cognitive dimensions, implying that patients and family members perceive and report cancer pain based on these factors. The study reported here investigated the relationship between specific knowledge and attitudes (cognitive factors), and patients' and family members' reports of pain due to cancer. The relationship between cognitive factors and reports of cancer pain was investigated in interviews with 122 patients and their family members. Pain was measured using the Brief Pain Inventory; knowledge and attitudes were measured using a form previously developed by the authors. Patients' and family members' reports of patient pain and performance status were highly correlated, although family members consistently reported more pain and disability. Using regression analysis, cognitive factors were strongly related to family reports of patients' pain (R2 = 0.27), but contributed little to explaining pain reported by patients themselves (R2 = 0.06). Improved understanding of patients' pain assessments depends on further investigation of other cognitive factors and of sensory and affective factors. Family members' assessments of pain are significantly related to appropriate knowledge and attitudes.