ABSTRACT
Widespread neuroinflammation in the central nervous system (CNS) of Alzheimer's disease (AD) patients, involving pro-inflammatory mediators such as complement components, might be responsible for AD associated behavioral symptoms such as anxiety. Vaccinia virus complement control protein (VCP) and curcumin (Cur) are the bioactive compounds of natural origin shown to inhibit the in-vitro complement activation. In order to develop complement regulatory compounds which could be delivered to the CNS by a non-invasive route, VCP, its truncated version (tVCP), and Cur were administered to Wistar rats intranasally. The distribution of these compounds in cerebrospinal fluid (CSF) was studied using an enzyme linked immunosorbent assay (ELISA), using VCP and tVCP as antigens and a modified fluorimetric method (Cur). VCP and tVCP were also detected in the olfactory lobes of the rat brain using immunohistochemical analysis. These compounds were then compared for their ability to attenuate the anxiety levels in APPswePS1δE9 mice using an elevated plus maze (EPM) apparatus. VCP treatment significantly improved the exploratory behavior and reduced the anxiety behavior in APPswePS1δE9 mice. tVCP however showed an opposite effect to VCP, whereas Cur showed no effect on the anxiety behavior of these mice. When these mice were subsequently tested for their cognitive performance in the Morris water maze (MWM), they showed tendencies to collide with the periphery of the walls of MWM. This unusual activity was termed "kissperi" behavior. This newly defined index of anxiety was comparable to the anxiety profile of the VCP and tVCP treated groups on EPM. VCP can thus be delivered to the CNS effectively via intranasal route of administration to attenuate anxiety associated with AD.
Subject(s)
Alzheimer Disease/complications , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anxiety/etiology , Anxiety/therapy , Curcumin/therapeutic use , Viral Proteins/therapeutic use , Administration, Intranasal , Alzheimer Disease/cerebrospinal fluid , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism , Animals , Anti-Inflammatory Agents, Non-Steroidal/cerebrospinal fluid , Anxiety/immunology , Complement System Proteins/genetics , Complement System Proteins/metabolism , Curcumin/metabolism , Disease Models, Animal , ELAV Proteins/genetics , Enzyme-Linked Immunosorbent Assay/methods , Humans , Maze Learning/drug effects , Mice , Mice, Transgenic , Presenilin-1/genetics , RatsABSTRACT
A prospective study was undertaken over a period of six months to determine the spectrum of infection, sensitivity of organisms isolated, and suitability of antibiotics chosen in 520 consecutive patients admitted to a paediatric unit. Culture and sensitivity of stool, urine and blood yielded 752 isolates; in 147 cases, more than one pathogen was isolated from the same or different sites. High rates of resistance to chloramphenicol, ampicillin, and kanamycin were seen in salmonellae other than Salmonella typhi, which differed in retaining its original sensitive susceptibility profile. Most Enterobacteria were sensitive to gentamicin. Penicillin-resistance was seen in 9% of meningococci, and several Haemophilus influenzae strains (20%) were resistant to ampicillin. Methicillin-resistance was encountered in 13% of Staphylococcus aureus strains and 17% of pneumococci were resistant to penicillin G. The sensitivity pattern of organisms isolated was probably directly related to widespread use of antibiotics.
