Calcitonin gene-related peptide is present in mammalian cerebrovascular nerve fibres and dilates pial and peripheral arteries

Calcitonin gene-related peptide (CGRP) is a novel 37-amino acid peptide occurring in neurones within sensory ganglia, in brain stem, as well as in the walls of blood vessels of peripheral organs. Pial arteries of cat showed a well-developed supply of CGRP-positive nerve fibres. The peptide was found to be a potent dilator of both pial and peripheral vessels of rabbit and cat, and of pial vessels from man. The dilatory effect was independent of the vascular endothelium and was not mediated through adrenergic, cholinergic or histaminergic smooth muscle receptors. The neurogenic vasoconstriction induced by electrical field stimulation was temporarily inhibited by CGRP, as studied in central ear arteries from rabbits. The results suggest that CGRP is a transmitter or modulator playing a role in the regulation of vascular tone.     

Excitatory amino acids and cerebrovascular tone

Levels of excitatory amino acids in the brain extracellular fluid compartment rise during pathological conditions in the brain such as ischaemia, anoxia and epilepsy. One such amino acid, glutamate, is present in sensory nerve fibres innervating, for example, cerebral vessels. Enhanced levels of circulating glutamate and aspartate are found in migraine sufferers. The present study examined whether excitatory amino acids, in concentrations found in the brain extracellular fluid compartment during pathological conditions, exert a direct effect on cerebrovascular tone. As tested in flow-regulating pial arteries from rat, cat and man, no such constrictive or dilatory effect was obtained.     

Lack of neural control and reactivity to vasoactive agents in malignant glioma arteries

Vessels in malignant brain tumors have a defective blood-brain barrier. It is important to know if tumor vessels respond to vasoactive agents, since systemic administration of vasodilatory agents together with chemotherapy could increase the access of these drugs to the tumor. It was found that arteries in human malignant gliomas have no neural control and are totally nonreactive to various vasoactive agents. The vessels lose their reactivity within 1 to 2 mm outside the visible tumor front.     

The effects of indomethacin on intracranial pressure,cerebral blood flow and cerebral metabolism in patients with severe head injury and intracranial hypertension

Summary In five head-injured patients with cerebral contusion and oedema in whom it was not possible to control intracranial pressure (ICP) (ICP>20 mmHg) by artificial hyperventilation (PaCO₂ level 3.5–4.0 kPa) and barbiturate sedation, indomethacin was used as a vasoconstrictor drug. In all patients, indomethacin (a bolus injection of 30 mg, followed by 30 mg/h for seven hours) reduced ICP below 20 mmHg for several hours. Studies of cerebral circulation and metabolism during indomethacin treatment showed a decrease in CBF at 2h. After 7h, ICP remained below 20 mmHg in three patients, and these still had reduced CBF. In the other patients a return of ICP and CBF to pretreatment levels was observed. In all patients indomethacin treatment was followed by a fall in rectal temperature. These results suggest that indomethacin due to its cerebral vasoconstrictor and antipyretic effect should be considered as an alternative for treatment of ICP-hypertension in head-injured patients.Presented at the Fifth Nordic CBF Symposium, Lund, Sweden, 21–22 May 1990.     

Railway noise annoyance and the importance of number of trains, ground vibration, and building situational factors

Internationally accepted exposure-response relationships show that railway noise causes less annoyance than road traffic and aircraft noise. Railway transport, both passenger and freight transport, is increasing, and new railway lines are planned for environmental reasons. The combination of more frequent railway traffic and faster and heavier trains will, most probably, lead to more disturbances from railway traffic in the near future. To effectively plan for mitigations against noise and vibration from railway traffic, new studies are needed to obtain a better basis of knowledge. The main objectives of the present study was to investigate how the relationship between noise levels from railway traffic and general annoyance is influenced by (i) number of trains, (ii) the presence of ground borne vibrations, and (iii) building situational factors, such as orientation of balcony/patio and bedroom window. Socio-acoustic field studies were executed in residential areas; (1) with relatively intense railway traffic; (2) with strong vibrations, and; (3) with the most intense railway traffic in the country. Data was obtained for 1695 respondents exposed to sound levels ranging from L(Aeq,24h) 45 to 65 dB. Both number of trains and presence of ground-borne vibrations, and not just the noise level per se, are of relevance for how annoying railway noise is perceived. The results imply that, for the proportion annoyed to be equal, a 5 - 7 dB lower noise level is needed in areas where the railway traffic causes strong ground-borne vibrations and in areas with a very large number of trains. General noise annoyance was twice as high among residents in dwellings with balcony / patio oriented towards the railway and about 1.5 times higher among residents with bedroom windows facing the railway.     

Counterregulatory responses to postprandial hypoglycemia after Roux-en-Y gastric bypass

BackgroundPostbariatric hypoglycemia (PBH) is a potentially serious complication after Roux-en-Y gastric bypass (RYGB), and impaired counterregulatory hormone responses have been suggested to contribute to the condition.ObjectivesWe evaluated counterregulatory responses during postprandial hypoglycemia in individuals with PBH who underwent RYGB.SettingUniversity hospital.MethodsEleven women with documented PBH who had RYGB underwent a baseline liquid mixed meal test (MMT) followed by 5 MMTs preceded by treatment with (1) acarbose 50 mg, (2) sitagliptin 100 mg, (3) verapamil 120 mg, (4) liraglutide 1.2 mg, and (5) pasireotide 300 μg. Blood was collected at fixed time intervals. Plasma and serum were analyzed for glucose, insulin, glucagon, epinephrine, norepinephrine, pancreatic polypeptide (PP), and cortisol.ResultsDuring the baseline MMT, participants had nadir blood glucose concentrations of 3.3 ± .2 mmol/L. At the time of nadir glucose, there was a small but significant increase in plasma glucagon. Plasma epinephrine concentrations were not increased at nadir glucose but were significantly elevated by the end of the MMT. There were no changes in norepinephrine, PP, and cortisol concentrations in response to hypoglycemia. After treatment with sitagliptin, 8 individuals had glucose nadirs <3.2 mmol/L (versus 4 individuals at baseline), and significant increases in glucagon, PP, and cortisol responses were observed.ConclusionsIn response to postprandial hypoglycemia, individuals with PBH who underwent RYGB only had minor increases in counterregulatory hormones, while larger hormone responses occurred when glucose levels were lowered during treatment with sitagliptin. The glycemic threshold for counterregulatory activation could be altered in individuals with PBH, possibly explained by recurrent hypoglycemia.     

Endothelial negative surface charge areas and blood-brain barrier function

Recent evidence points to the negative surface charge of the luminal endothelial membrane of brain vessels as one determinant for morphologic blood-brain barrier function. The present study evaluates, in awake rats, how barrier function is affected by the polycation protamine to neutralize the negatively charged groups. High local doses of protamine, as infused intracarotideally, are able to substantially impair barrier capacity against albumin and inulin, which normally do not pass the blood-brain barrier. Evidence is presented that it is the positive charge of protamine that is a major factor underlying the barrier opening. However, when comparing the barrier opening obtained by corresponding concentration of the polycation lysine, it was obvious that another property of protamine contributed. This property was not linked to hyperosmolar, hypertensive or vasodilatory barrier opening, but may be a direct, cytotoxic effect of protamine. It is discussed whether barrier opening through transendothelial vesicular or channel transport occurs only at locations on the cell membrane deprived of negative surface charge areas.     

Endothelin is a potent constrictor of human intracranial arteries and veins

Endothelin, a peptide produced in endothelial cells, was found to be a potent constrictor of human pial arteries through a direct, slow action on the smooth muscle cell, with a pD2 value of 8.54. It was less potent as a constrictor in pial veins (pD2 7.80) and in branches of the middle meningeal artery and superficial temporal artery (pD2 7.61 and 7.77). The major component of the contractile response in the arteries comprises an effect on potential-operated calcium channels, as evidenced by tests with nimodipine. Endothelin may regulate intracranial vessels tonically during physiological as well as pathophysiological conditions.     

Chronic nicotine treatment eliminates asymmetry in striatal glucose utilization following unilateral transection of the mesostriatal dopamine pathway in rats

Partial hemitransection was performed through a knife lesion at the meso-diencephalic level in rats to sever the mesostriatal dopamine system. During the subsequent 2 weeks the animals received 0.125 mg/kg/h of nicotine continuously via an osmotic minipump implanted s.c. To achieve prompt high nicotine levels, 4 i.p. injections of 0.5 mg/kg nicotine were, in addition, given during the first 2 h following the lesion. The total treatment corresponded to a mean plasma level of 50 ng/ml nicotine, measured at the end of the experiment. Control animals received corresponding volumes of 0.9% saline. Quantitative autoradiographic analysis of the glucose utilization in the caudate nucleus using Sokoloff's [14C]2-deoxyglucose method demonstrated a 16% side-to-side difference in the lesioned control animals, whereas the asymmetry was counteracted by the nicotine treatment. Although there was an overall tendency to a lower rate of glucose utilization (by 6%) in the nicotine-treated animals compared to the controls receiving saline only, the difference was not statistically significant. The eliminated asymmetry probably reflects an increased survival of the dopamine neurons and/or of striatal nerve cells on the lesioned side due to protective effects of nicotine resulting from desensitization of nicotinic-type cholinergic receptors following continuous administration of the drug.