Biochemical Characterization of α-Adrenergic Receptors in Human Brain and Changes in Alzheimer-Type Dementia

Abstract Using ligand binding techniques, we studied α-adrenergic receptors in brains obtained at autopsy from seven histologically normal controls and seven patients with histopathologically verified Alzheimer-type dementia (ATD). Binding of the α-adrenergic antagonists [³H]prazosin and [³H]yohimbine to membranes of human brains exhibited characteristics compatible with α₁- and α₂-adrenergic receptors, respectively. Binding of both ligands was saturable and reversible, with dissociation constants of 0.15 nM for [³H]prazosin and 5.5 nM for [³H]yohimbine. [³H]Prazosin binding was highest in the hippocampus and frontal cortex and lowest in the caudate and putamen in the control brains. [³H]Yohimbine binding was highest in the nucleus basalis of Meynert (NbM) and frontal cortex and lowest in the caudate and cerebellar hemisphere in the control brains. Compared with values for the controls, [³H]prazosin binding sites were significantly reduced in number in the hippocampus and cerebellar hemisphere, and [³H]yohimbine binding sites were significantly reduced in number in the NbM in the ATD brains. These results suggest that α₁ and α₂-adrenergic receptors are present in the human brain and that there are significant changes in numbers of both receptors in selected regions in patients with ATD.     

A comparison of the translational diffusion of a normal and a membrane-spanning lipid in Lα phase 1-palmitoyl-2-oleoylphosphatidylcholine bilayers

We have used the fluorescence recovery after photobleaching technique to study the translational diffusion, in L phase multibilayers of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), of fluorescent derivatives of 1-palmitoyl-2-oleoylphosphatidylethanolamine (NBD-POPE) and a membrane-spanning phosphatidylethanolamine (NBD-MSPE). The latter derivative was prepared from a membrane-spanning glycerol-dialkyl-glycerol tetraether lipid isolated from the thermophilic and acidophilic archaebacterium Sulfolobus solfataricus. The translational diffusion was examined between about 15° and 45°C. It is shown that over this temperature range the translational diffusion coefficient for NBD-MSPE is 2/3 that for NBD-POPE which spans only one monolayer of the bilayer. The result is interpreted in terms of existing models for translational diffusion in lipid membranes.Abbreviations D _t translational diffusion coefficient - FRAP fluorescence recovery after photobleaching - MSPE a membrane-spanning phosphatidylethanolamine derived from a glycerol-dialkyl-glycerol tetraether lipid isolated from Sulfolobus solfataricus - NBD 4-nitrobenz-2-oxa-1,3-diazolyl - PE phosphatidylethanolamine - POPC 1-palmitoyl-2-oleoylphosphatidylcholine - POPE 1-palmitoyl-2-oleoylphosphatidylethanolamine     

Carbohydrates,lipids and lipoproteins and islet changes in diabetes with superimposed myocardial infarction

Short-term metabolic and concomitant morphologic effects of streptozotocin diabetes on isoproterenol-induced myocardial infarction was studied in Wistar rats, Of particular significance was the observation that myocardial infarction in concert with diabetes brought about a distinctive exacerbation of the severity and complexity of the histopathological lesions. Of all the biochemical parameters, serum glucose and free fatty acids registered maximum elevation and serum lactate and cardiac glycogen levels a maximum reduction. Among the lipoproteins, an inverse relationship was found between high density lipoproteins and low density and very low density lipoproteins; while high density lipoproteins, ratio of high density lipoprotein to low density lipoprotein and the percentage of high density lipoprotein were decreased, there was a significant increase in low density lipoprotein concentration and percentage values of low density and very low density lipoproteins. In diabetes, the B cell of the endocrine pancreas depicted selective necrosis. Loss of insulin granules and wide-spread necrobiosis of cellular elements of the pancreatic islets were observed, respectively, in myocardial infarction and in diabetes plus myocardial infarction combinations. Pathological evidence of chemical-induced mild toxicity was present in the exocrine parenchyma. Mitotic features and the presence of centroacinar cells in the damaged Langerhans’ islets supposedly formed the basis of regeneration of the tissue in diabetes, with or without vascular complications     

Cardiac copper,magnesium, and zinc in recent and old myocardial infarction

X-ray fluorescence spectrometry and atomic absorption spectrometry were used in a quantitative study of zinc, copper, and magnesium in 71 postmortal human hearts. Samples were obtained from individuals who had demonstrated no previous clinical or subsequent pathological findings of myocardial infarction and from victims of a recent or an old infarction. A significant difference (p<0.001) in the elemental levels was observed between the noninfarct and the recent infarct groups. The noninfarct group had higher cardiac levels of all three elements. However, the difference in elemental concentrations between the noninfarct and the old-infarct groups was not significant. Cardiac levels of zinc (p<0.001) and copper (p<0.01) were significantly greater in the old-infarct group than in the recent-infarct group. Magnesium levels were higher in the recent-and-old-infarct group than in the recent infarct group (p<0.01). It is possible that the elements are redistributed during myocardial infarction, and that uptake of these elements (from the serum pool) by the heart may be important in maintaining myocardial integrity and function.     

The Genera of the Subfamily Heteroderinae (Nematoda: Tylenchoidea) with a Description of Two New Genera

The family Heteroderidae, its two subfamilies Heteroderinae and Meloidogyninae and the nominal genera of Heteroderinae (Heterodera Schmidt, 1871; Meloidodera Chitwood, Hannon &Esser, 1956; and Cryphodera Colbran, 1966) are rediagnosed. Meloidoderita Pogosyan, 1966 is considered a genus inquirenda. Two new genera from southern California are described in the subfamily Heteroderinae. A key to the genera, illustrations and a phylogeny of the Heteroderinae are proposed.     

Hyolith guts in the Cambrian of northern Australia -turning hyolithomorphs upside down

A single specimen of the early Middle Cambrian (Ordian) orthothecimorph hyolith Gudugu-wan hardmani with preserved gut filling has been discovered in the Montejinni Limestone, Wiso Basin, northern Australia. This represents only the eighth such occurrence worldwide. The specimen is unique among orthothecimorphs in retaining the gut filling in combination with the external mould of the operculum and invites revision of the accepted soft-part recon struction in this group, whereby the opercular lateral processes are now recognized to be ventral. Thus orthothecimorph conchs, if horizontal in life, would have been oriented ventral side down, while hyolithomorphs adopted the reverse orientation: horizontal, ventral side up.     

Meteorological factors and the time of onset of chest pain in acute myocardial infarction

Analysis of the time of onset of chest pain in 2254 patients with a myocardial infarction admitted to a coronary care unit in Leicester during a 10-year period shows an association with temperature and humidity. During both the most cold and humid times of the year, the relationship is a strong one. A generalized linear model with a log link was used to fit the data and the backward elimination selection procedure suggested a humid, cold day might help to trigger the occurrence of myocardial infarction. In addition, cold weather was found to have a stronger effect on the male population while those men aged between 50 and 70 years were more sensitive to the effect of high humidity.     

Human aging brain disorders: Role of antioxidant enzymes

In order to investigate the role of two free radical detoxificant enzymes in patients with aging brain disorders, superoxide dismutase (SOD) and catalase (CAT) activities have been measured in blood from male and female human patients of different ages with several types of aging brain disorders. When compared with activities in the normal population, we have detected: 1) SOD and CAT activities are decreased in patients with Parkinson disease. 2) SOD activity seems to be normal and CAT activity is decreased in patients with dementia. 3) In the patients with stroke, SOD activity is normal, while CAT activity is decreased. SOD activity was measured in red blood cells using the Minami and Yoshikawa method. CAT activity was measured in hemolysates by the method of Aebi. We can conclude that SOD and CAT activities in patients with Parkinson disease are decreased.     

Early after-depolarisations induced by noradrenaline may be initiated by calcium released from sarcoplasmic reticulum

We investigated the effect of 10^–8 M noradrenaline (NA) on [Ca²⁺], and electrical activity of single myocytes of guinea-pig ventricular myocardium loaded with Indo 1-AM. Membrane potential was recorded by means of the patch electrode and patch amplifier set to the current clamp mode. Cells were stimulated at a rate of 30/min by 3 ms pulses of the current injected through the recording electrode. Superfusion of NA resulted in slight shortening of action potentials (APs), increase in rate of rise and amplitude of the respective Ca²⁺ transients, and appearance of secondary Ca²⁺ transients of two kinds: 1. appearing before repolarisation of AP and decay of the preceding Ca²⁺ transient were completed and 2. appearing between the APs. We named them early after-transients (EAT) and delayed after-transients (DAT), respectively. Without any additional intervention EATS caused some prolongation of APs duration and DATs resulted in subthreshold delayed after-depolarisations (DADS). When sarcolemmal K⁺ conductance was decreased by tetraethylammonium (TEA) in the patch electrode or 20 M BaCl₂ in the Tyrode solution, EATs initiated early after depolarizations (EADs) and DATs initiated suprathreshold DADs triggering full-sized APs. Superfusion of 30.0 mM Na⁺ (replaced with LiCl) resulted in reduction of AP duration by -70% and appearance of DATs. Also, the frequent multiple oscillations of Ca ²⁺ concentration were often observed. Neither DATs nor the oscillations had any affect on electrical activity of the cells. Their electrogenicity could not be increased by TEA or 20.0 M Ba²⁺. EATs and DATs and their respective EADs and DADs could not be initiated by NA or low Na⁺ superfusion in the cells pretreated with 2 × 10^–7 M thapsigargin, a selective blocker of Ca²⁺-ATPase of sarcoplasmic reticulum (SR). We conclude that in contrast to the current hypothesis, EADs can be initiated by Ca²⁺ released early in the cardiac cycle from the overloaded SR, and that electrogenicity of both types of Ca²⁺ oscillations critically depends on the sarcolemmal K⁺ conductance.