123I-amphetamine-SPECT in classical migraine and migraine accompagnée

Migraine is considered to be a functional neurological disorder. In classical migraine (headache associated with prodromal visual field disturbances) and migraine accompagnée (headache associated with transient neurological symptoms), disturbances of cerebral blood flow and amine metabolism are thought to be pathogenetic factors. However, conventional methods of neuroimaging (CAT, NMR) usually do not yield any pathological findings in patients. Since 123I-iodoamphetamine (123I-IMP) crosses the intact blood brain barrier, 123I-IMP-SPECT is used for the assessment of cerebral perfusion in various neurological diseases, including functional disorders. 123I-IMP-SPECT was performed on 5 patients with classical migraine and 18 patients with migraine accompagnée. At the time of investigation, all patients were symptom-free. Cerebral blood flow was decreased in all patients with migraine accompagnée, and often corresponded to the site of headache as well as to the topography of transient neurological symptoms. This reduction was most obvious in a patient with persisting neurological symptoms. Most patients with classical migraine, however, did not show any alteration of cerebral perfusion. It appears that migraine--and in particular migraine accompagnée--is characterized by a permanent alteration not only of cerebral blood flow but also of neuronal activity. Migraine attacks may occur in connection with exacerbations of preexisting metabolic alterations.     

The monoclonal antibody Alz-50, used to reveal cytoskeletal changes in Alzheimer's disease, also reacts with a large subpopulation of somatostatin neurons in the normal human hypothalamus and adjoining areas

The monoclonal antibody Alz-50 is directed against Alzheimer's disease-related modified tau proteins and reveals cytoskeletal changes, i.e. neurofibrillary tangles and dystrophic neurites. The present study shows that, in the hypothalamus of non-demented control subjects, this same antibody gives a distinctive staining pattern of a subpopulation of somatostatin neurons and beaded fibers. Furthermore, Alz-50 occasionally recognizes somatostatin-containing cell bodies and dystrophic neurite-like fibers in the (neuritic) senile plaques of AD patients. These observations have direct consequences for the interpretation of Alz-50 staining in diagnostic usage and for the assessment of Alzheimer's disease-like changes induced by β-amyloid in experimental animal brains. On dot spotting, Alz-50 was found to bind to a number of fragments from the somatostatin precursor, of which somatostatin_15–28 stained best. Preadsorption of Alz-50 by somatostatin_15–28, as well as other specificity tests, failed, however, to provide any clue to the nature of the unknown compound(s) stained in the control hypothalamus.     

The ubiquitin ligase Rnf6 regulates local LIM kinase 1 levels in axonal growth cones

LIM kinase 1 (LIMK1) controls important cellular functions such as morphogenesis, cell motility, tumor cell metastasis, development of neuronal projections, and growth cone actin dynamics. We have investigated the role of the RING finger protein Rnf6 during neuronal development and detected high Rnf6 protein levels in developing axonal projections of motor and DRG neurons during mouse embryogenesis as well as cultured hippocampal neurons. RNAi-mediated knock-down experiments in primary hippocampal neurons identified Rnf6 as a regulator of axon outgrowth. Consistent with a role in axonal growth, we found that Rnf6 binds to, polyubiquitinates, and targets LIMK1 for proteasomal degradation in growth cones of primary hippocampal neurons. Rnf6 is functionally linked to LIMK1 during the development of axons, as the changes in axon outgrowth induced by up- or down-regulation of Rnf6 levels can be restored by modulation of LIMK1 expression. Thus, these results assign a specific role for Rnf6 in the control of cellular LIMK1 concentrations and indicate a new function for the ubiquitin/proteasome system in regulating local growth cone actin dynamics.     

The Kallikrein-Kinin system and muscle metabolism—Clinical aspects

The influence of synthetic bradykinin (BK) on disturbed protein and carbohydrate metabolism was studied in chemical and manifest maturity-onset diabetics, in surgical patients and in alloxan diabetic rats. BK,mixed with insulin and injected subcutaneously twice daily in alloxan diabetic rats lowered the morning blood glucose concentration in a dose-dependent way, whereas in a control group treated with insulin only no decrease was seen. Accelerated local blood flow or enhanced vascular permeability as a cause of increased glucose uptake could be ruled out by control experiments using papaverine and eledoisin. Better metabolic control in the BK/insulin-treated group was also indicated by lower arterial levels of free fatty acids and of -hydroxybutyrate, normalized hepatic glycogen content and better growth of body weight. In healthy man an intravenous infusion of BK (80 g/h) did not influence normal fasting blood glucose concentrations, whereas elevated glucose levels in maturity-onset diabetics were continuously reduced within 100 min by 12.2±1.4%. A comparable diabetic group receiving saline alone showed no spontaneous drop of blood glucose concentration. An improvement of pathological carbohydrate metabolism by infusion of BK i.v. could also be demonstrated using the intravenous glucose tolerance test in chemical and manifest maturity-onset diabetics and in surgical patients: in all groupsk values of the glucose tolerance test were significantly increased by BK. This effect was neither due to stimulated insulin release nor to changed glucose pool or to increased renal glucose loss, which was even reduced by BK. Interestingly, normalk values in healthy volunteers were not further improved by BK. A stimulated protein breakdown, which occurs after surgery due to peripheral insulin resistance, can also be restricted by intravenous infusion of BK: in surgical patients urinary nitrogen excretion was reduced by 50% during infusion of BK and was accelerated again after cessation of the infusion. These results indicate that BK can improve the efficacy of exogenous insulin in insulin-deficient animals and depressed insulin sensitivity in maturity-onset diabetics and surgical patients.     

The direct early diagnosis of cystic fibrosis by the detection of the deltaF508 CFTR gene mutation in a prematurely delivered boy

The suspicion of prenatal meconium ileus syndrome was raised in a pregnancy in a family with no history of cystic fibrosis because of significantly higher maternal serum alpha-fetoprotein in the 16th and 19th week of gestation, dispersed areas with increased echogenity in the fetal abdomen, slight fetal ascites in the 24th-25th weeks of gestation, decreased amniotic fluid gamma-glutamyltranspeptidase (GGT) activity and alpha-fetoprotein level in the 25th-26th weeks, and normal 46,XY karotype of the fetus. The detection of a homozygous deltaF508 cystic fibrosis transmembrane regulator (CFTR) gene mutation, by means of PCR from a small amount of white blood cells and urine sediment cells, substantiated the diagnosis of cystic fibrosis in a prematurely delivered boy in the 28th week of gestation. The repeated sweat test was unsuccessful. The autopsy examination confirmed the diagnosis of cystic fibrosis. Fetal meconium ileus syndrome was complicated by peritonitis and by formation of a meconium pseudocyst. Direct PCR typing improves postnatal diagnostic possibilities in the early neonatal period in prematurely delivered babies when the sweat test is difficult to perform.     

Flattening the quality of life curve? A prospective person-centred study from Norway amid COVID-19

Quality of Life Research - We examined multidimensional, heterogeneous reactions to the COVID-19 pandemic and associated measures to provide further insights into the developmental processes of...     

Evidence for metabolic and functional discrimination of sterols by Phytophthora cactorum

When fed 10 ppm of one of the following sterols: cholesterol (cholest-5-en-3β-ol), wingsterol (21-isopentylcholesterol), desmosterol [cholesta-5,24(25)-dien-3β-ol], 24-methylenecholesterol [ergosta-5,24(28)-dien-3β-ol], or fucosterol [stigmasta-5,24(28)-dien-3β-ol], the pathogenic fungus Phytophthora cactorum, which is naturally unable to epoxidize squalene, accumulated each of the test compounds to similar levels. Fucosterol, the only sterol metabolized, was reduced to yield 24-ethylcholesterol. All the sterols tested induced the formation of sex structures. Fertilization and subsequent maturation of oospores capable of germination occurred only with the naturally occurring sterols. Wingsterol treatments resulted in aborted oospores. None of the sterols tested was inhibitory to growth, measured as changes in the 21-day mycelial dry weight. The results are consistent with the view that the accumulated sterol functions to regulate the life cycle of P. cactorum. However, the metabolism and kinds of recognition of the sterol molecule, in terms of uptake and effects on growth and induction of the various sexual events, contrast sharply with what is known for other oomycetous fungi such as Achlya and Saprolegnia. This implies that the evolutionary histories of the Oomycetes may be different.     

Magnetic Resonance Angiography of the Abdominal Aorta

Magnetic resonance angiography (MRA) of the abdominal aorta was performed in 36 patients using the "bright-blood" technique on the basis of a series of flow-compensated breath-hold 2 D-GE pulse sequences. Diverse diseases included complete occlusion, stenosis, atherosclerotic or dissecting aneurysm and renal artery stenosis. Coronal and axial projection angiograms [maximum intensity projection (MIP) algorithm] and individual GE images were compared with DSA and contrast-enhanced computed tomography (CT). Our data showed a good correlation of MR and digital subtraction arteriography (DSA) or CT resp. in all cases, when both rotating MIP angiograms and individual GE images were analyzed. Thus, MR is suggested to be a useful noninvasive diagnostic method for the abdominal aorta, particularly in preoperative staging of aneurysms, aortic occlusive disease, and stenosis of the proximal main renal artery. Drawbacks of the method are a signal loss in slow or turbulent flow conditions, and unsatisfactory spatial resolution in small vessels.     

Complex regional pain syndrome and dysautonomia in a 14‐year‐old girl responsive to therapeutic plasma exchange

Reflex sympathetic dystrophy, also known as complex regional pain syndrome (CRPS), has recently been shown to be associated with autoantibodies against β2‐adrenergic and muscarinic M2 receptors. In addition to pain and sudomotor/vasomotor symptoms, dysautonomia is also observed in a subset of CRPS patients. Despite its severity, there are few effective therapies for CRPS described to date. We report a case of a 14‐year‐old girl with CRPS of her right leg and dysautonomia (gastroparesis, postural tachycardia) refractory to multiple therapies, successfully treated with therapeutic plasma exchange (TPE) with albumin replacement. The patient, who has serum anti β2‐adrenergic and muscarinic M2 receptor autoantibodies in addition to nicotinic acetylcholine receptor ganglionic autoantibodies, underwent an initial course of five TPEs over a 2‐week period. She demonstrated a clinical response to TPE as manifested by a rapid improvement in her fatigue and gastroparesis, with a gradual yet significant improvement in her leg pain and sudomotor/vasomotor flares. Following the loading procedures, the patient was treated with rituximab. She continues to require periodic TPE to maintain a remission, with additional immunosuppression being considered long term. Although further studies are needed, TPE (in combination with immunosuppression) may be an appropriate therapy for CRPS patients with detectable autoantibodies, as it is for better characterized diseases with autoantibodies against neuronal surface receptors such as myasthenia gravis or Lambert Eaton myasthenic syndrome. J. Clin. Apheresis 31:368–374, 2016. © 2015 Wiley Periodicals, Inc.