Microglia are more susceptible than macrophages to apoptosis in the central nervous system in experimental autoimmune encephalomyelitis through a mechanism not involving Fas (CD95)

Morphological studies have shown that macrophages and microglia undergo apoptosis in the central nervous system (CNS) in acute experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. To assess the relative levels of macrophage and microglial apoptosis, and the molecular mechanisms involved in this process, we used three-colour flow cytometry to identify CD45lowCD11b/c+ microglial cells and CD45highCD11b/c+ macrophages in the inflammatory cells isolated from the spinal cords of Lewis rats 13 days after immunization with myelin basic protein (MBP) and complete Freund's adjuvant. Simultaneously, we analyzed the DNA content of these cell populations to assess the proportions of cells undergoing apoptosis and in different stages of the cell cycle or examined their expression of three apoptosis- regulating proteins, i.e. Fas (CD95), Fas ligand (FasL) and Bcl-2. Microglia were highly vulnerable to apoptosis and were over-represented in the apoptotic population. Macrophages were less susceptible to apoptosis than microglia and underwent mitosis more frequently than microglia. The different susceptibilities of microglia and macrophages to apoptosis did not appear to be due to variations in Fas, FasL or Bcl- 2 expression, as the proportions of microglia and macrophages expressing these proteins were similar, and were relatively high. Furthermore, in contrast to T cell apoptosis, apoptosis of microglia/macrophages did not occur more frequently in cells expressing Fas or FasL, or less frequently in cells expressing Bcl-2. These results indicate that the apoptosis of microglia and CNS macrophages in EAE is not mediated through the Fas pathway, and that Bcl-2 expression does not protect them from apoptosis. Expression of FasL by macrophages and microglia may contribute to the pathogenesis and immunoregulation of EAE through interactions with Fas+ oligodendrocytes and Fas+ T cells. The high level of microglial apoptosis in EAE indicates that microglial apoptosis may be an important homeostatic mechanism for controlling the number of microglia in the CNS following microglial activation and proliferation.      

Influence of saccharide length on polysaccharide appetite in the rat

The appetite of female rats for saccharides of different chain lengths was assessed in brief (5-min) one-bottle acceptance and two-bottle preference tests. The saccharides (and their lengths in glucose units) included glucose (1), maltose (2), maltotriose (3), maltooligosaccharide (4-8), maltopolysaccharide (average length 43), and Polycose (1 to 30+); 0.0125 and 0.025 molar solutions of these saccharides were tested. The results revealed that the rats' order of preference for these saccharides was as follows: maltooligosaccharide greater than maltotriose = maltose greater than glucose; and maltooligosaccharide greater than Polycose = maltopolysaccharide greater than maltose. Thus, as saccharide chain length increased from 1 to 4-8 glucose units palatability increased, but with further increases in chain length palatability declined somewhat. Previous findings have suggested that rats have a "polysaccharide" taste receptor and the present results indicate that the receptor is maximally (or near-maximally) stimulated by saccharides of 4-8 glucose units in length.     

N-Mannich-Base Prodrugs of 5-Iodo-2′-deoxycytidine as Topical Delivery Enhancers

Two Mannich-base prodrugs of 5-iodo-2-deoxycytidine (5-IDC) have been synthesized. The prodrugs exhibit increased lipid solubility compared to 5-IDC and rapidly revert to 5-IDC in buffer. One of the prodrugs delivered about twice as much 5-IDC from isopropyl myristate (IPM) through hairless mouse skin in diffusion-cell experiments as did 5-IDC from IPM. Subsequent applications of theophylline/ propylene glycol onto the diffusion cells to determine the effect of prodrug/IPM, 5-IDC/IPM, or IPM on the resistance of the skins to subsequent applications showed that the prodrug/IPM had no more effect than IPM itself.     

Long-term Effects of Adolescent Substance Use Prevention on Participants,Partners, and their Children: Resiliency and Outcomes 15 Years Later During the COVID-19 Pandemic

Prevention Science - We examined whether participation in adolescent substance use prevention programming can enhance long-term resilience into adulthood such that individuals were better able to...     

Influencing prescribing practices and associated outcomes utilizing the drug use evaluation process

Influencing prescribing practices and the implementation of pharmaceutical care utilizing the drug use evaluation (DUE) process at a 891-bed teaching hospital are described. The DUE program has been structured to provide for significant pharmacy involvement while maintaining medical staff responsibility as outlined by the Joint Commission on Accreditation of Healthcare Organizations. A multidisciplinary approach is used to identify problems and develop prescribing criteria and educational initiatives. Pharmacists provide drug therapy monitoring and engage in clinical interventions and documentation of outcomes on a daily basis. DUE program pharmacists help target possible interventions, assure monitoring and outcome documentation, and compile results of all initiatives for reporting purposes to the medical staff and quality assessment program. Specific performance compliance and problems are identified and incorporated into the credentialing process. Corrective measures are determined by the Pharmacy and Therapeutics (P&T) Subcommittee with subsequent actions carried out by peer physicians. The net result is a positive influence on prescribing practices that improves the appropriate and effective use of drugs and improves patient outcomes.     

Valproate in Bipolar Disorder: Case Examples From a Family Practice

Valproate, an antiepileptic drug, is useful in the management of various nonepileptic disorders. It is an effective and generally well-tolerated medication for the treatment of bipolar disorder and has been approved by the Food and Drug Administration for use in manic states. Studies also suggest that it is effective in other bipolar spectrum illnesses. This report describes 2 clinical cases of DSM-IV bipolar disorder where valproate provided robust, sustained relief of mood symptoms. In the first case, valproate was chosen for initial therapy in a bipolar patient suffering from a mixture of hypomanic and depressive symptoms. In the second case, valproate replaced lithium in the management of a patient with an incomplete response to lithium plus an antidepressant. This report addresses relevant clinical issues and includes a brief review of the clinical pharmacology of valproate.     

Radiographic techniques to evaluate paintings

Radiographic techniques may be helpful in evaluation of the condition of paintings for their restoration, preservation, and occasionally to determine their authenticity. On the basis of experience with several of these procedures, the utility of each method is described in reference to specific "diagnoses" regarding paintings. Radiographic techniques have several advantages over other methods; they are nondestructive, they may be used to survey the entire painting, and they are subject to quantitative and serial analysis.