Development of inflammation after application of mustard oil or glutamate to the rat temporomandibular joint

Application of the small-fibre excitant and inflammatory irritant mustard oil or the excitatory amino-acid receptor agonist glutamate to the rat temporomandibular joint (TMJ) region evokes similar changes in jaw-muscle activity, suggesting that peripheral application of glutamate may be nociceptive. Application of mustard oil to the TMJ region is also inflammatory, but, it is not clear if application of glutamate is equally inflammatory. In this study the extent of plasma-protein extravasation and oedema induced by mustard oil application to the TMJ region was compared with that induced by glutamate. Application of mustard oil resulted in plasma-protein extravasation into the TMJ tissues and oedema of the TMJ region. In contrast, glutamate did not cause plasma-protein extravasation or oedema.     

Ischemic preconditioning attenuates functional, metabolic, and morphologic injury from ischemic acute renal failure in the rat

Ischemic preconditioning has been shown to ameliorate injury due to subsequent ischemia in several organs. However, relatively little is known about preconditioning and the kidney. To address this, rats were randomized to control (C, N = 14), 2 min of ischemic preconditioning (P2 N = 10), 3 periods of 2 min of ischemia separated by 5 min periods of reflow (P2,3 N = 7), or three 5 min periods of ischemia separated by 5 min of reflow (P5,3 N = 6) prior to 45 min of bilateral renal ischemia followed by 24 hours of reperfusion. We observed a lower serum creatinine after 24 hours of reflow in P2, P2, 3 but not P5, 3 rats compared with C. Histology was examined in the C and P2, 3 groups and demonstrated less severe injury in the P2, 3 group. To gain insight into the mechanism by which preconditioning ameliorated ischemic injury, we performed near IR spectroscopy and 31P NMR spectroscopy. Based on near IR spectroscopy, the P2, 3 group had closer coupling of cytochrome aa3 redox state with that of hemoglobin during reflow. In the 31P NMR studies, the changes in ATP and pHi were similar during ischemia, but the P2, 3 group recovered ATP and pHi faster than C. These data suggest that ischemic preconditioning may ameliorate ischemic renal injury as assessed by functional, metabolic and morphological methods. The mechanism(s) by which this occurs requires additional study.     

Piracetam reverses hippocampal membrane alterations in Alzheimer's disease

Summary. The in vitro effects of piracetam treatment on the fluidity of membranes from the hippocampus of Alzheimer's Disease patients (AD) and non-demented controls were studied. Hippocampal membranes of AD patients showed a significant lower hydrocarbon core fluidity compared with membranes from elderly non-demented controls. Preincubation with piracetam enhanced the hydrocarbon core fluidity of hippocampal membranes from AD-patients as well as elderly controls in a concentration depending fashion, although the effect was more pronounced for the AD membranes. In the presence of piracetam, the difference of the membrane fluidity between AD and control membranes was not longer apparent. Received January 18, 1999; accepted April 13, 1999     

beta-amyloid deposition and neurofibrillary tangle formation in the olfactory bulb in ageing and Alzheimer's disease

Impaired olfaction, hyposmia or anosmia are part of the clinical phenotype in neurodegenerative disorders including Alzheimer's disease (AD). It has been proposed that the most severely affected areas are interconnected with the central olfactory system in contrast to the relative sparing of other sensory areas which lack olfactory connections. The pathology of the first synaptic relay in the olfactory pathway, the olfactory bulb (OB), has been studied in AD, but the results have been inconsistent. In order to define more fully the pathology of the OB, we analysed 15 AD and 15 control cases, using amyloid and tau immunohistochemistry on serial sections. This study demonstrates for the first time that all layers of the OB are severely affected in AD and in normal ageing. The principal effector cells of the OB, the mitral cells, developed neurofibrillary tangles (NFTs) both in AD and in controls. All the cases, with the exception of two of the controls, contained NFTs. Amyloid immunoreactivity was detected in diffuse, primitive, classical and compact deposits in AD, while five control cases contained mainly diffuse deposits. We did not find a correlation between amyloid deposition and NFT formation. Among the control cases, two contained neither amyloid nor NFTs, eight had NFTs but no amyloid and only five had both NFTs and amyloid. All the AD cases had NFT and amyloid deposition. Our data suggest that the earlier pathology in the OB is NFT formation and more than ten NFTs/section is compatible with 93.3% diagnostic accuracy for AD.     

Decreased phospholipase A2 activity in the brain and in platelets of patients with Alzheimer's disease

Phospholipase A₂ (PLA₂) is a key enzyme in the metabolism of membrane phospholipids. PLA₂ influences the processing and secretion of the amyloid precursor protein, which give rise to the -amyloid peptide, the major component of the amyloid plaque in Alzheimer's disease (AD). We investigated the PLA₂ activity in two samples: in post-mortem brains from 23 patients with AD and 20 non-demented elderly controls, and platelets from 16 patients with a diagnosis of probable AD, 13 healthy controls and 14 elderly patients with a major depression. In AD brains PLA₂ activity was significantly decreased in the parietal, and to a lesser degree in the frontal, cortex. Lower PLA₂ activity correlated significantly with an earlier onset of the disease, an earlier age at death and higher counts of neurofibrillary tangles and senile plaques. In platelets PLA₂ activity was also significantly reduced in the AD group as compared with healthy and depressed controls. The reduction of the enzyme activity in platelets correlated with an early disease onset and with the severity of cognitive impairment, indicating a relationship between abnormally low PLA₂ activity and a more severe form of the illness. The present results provide new evidence for a disordered phospholipid metabolism in AD brains and suggest that reduced PLA₂ activity may contribute to the production of amyloidogenic peptides in the disease. Further studies are needed to examine whether PLA₂ activity in platelets may be useful as a peripheral marker for a subgroup of patients with AD.     

Secondary prevention of excessive alcohol use: assessing the prospects of implementation

BACKGROUND: Alcohol risk and harm reduction is a public health approachthat goes beyond specialized treatments for alcoholism. Thegreatest potential for reducing alcohol risk and harm in a populationdepends on the extent to which health care practitioners usesecondary prevention programmes. OBJECTIVE: We aim to assess the factors that affect the prospects of disseminatingcomprehensive, secondary prevention programmes into mainstreampractice. METHOD: A decision balance was used to assess the prospects of practitionersimplementing comprehensive programmes systematically. The stages-of-changemodel provides perspectives about behaviour change with regardto patients, practitioners and practice settings. RESULTS AND CONCLUSIONS: Programme implementation is extremely unlikely given the currentorganization of health care settings. To maintain the use ofsuch programmes, we need to change the "unit of leverage" inthe system: from the clinical encounter—that is, practitionersworking with individual patients in a case-finding manner—toan organizational level—that is, the appropriate use ofmanagerial and information systems supporting health care settingsto identify at-risk patients systematically as they enter primarycare and hospital settings. With appropriate infrastructuresupport, practitioners will be able to fulfil the potentialfor as well as maintain the use of comprehensive, secondaryprevention programmes to reduce alcohol risk and harm in thepopulation. Keywords. Alcohol abuse, general practice, implementation, secondary prevention.