The novel hormone ghrelin is a potent orexigen that may counterbalance leptin. Ghrelin is the only secreted molecule requiring post-translational acylation with octanoic acid to ensure bioactivity. Ghrelin, predominantly derived from the stomach, may target neuroendocrine networks within the central nervous system (CNS) to regulate energy homeostasis. This would require ghrelin to cross the blood-brain barrier (BBB). In mice, we examined whether ghrelin crosses the BBB and whether its lipophilic side chain is involved in this process. We found that saturable systems transported human ghrelin from brain-to-blood and from blood-to-brain. Mouse ghrelin, differing from human ghrelin by two amino acids, was a substrate for the brain-to-blood but not for the blood-to-brain transporter and so entered the brain to a far lesser degree. des-Octanoyl ghrelin entered the brain by nonsaturable transmembrane diffusion and was sequestered once within the CNS. In summary, we show that ghrelin transport across the BBB is a complex, highly regulated bidirectional process. The direction and extent of passage are determined by the primary structure of ghrelin, defining a new role for the unique post-translational octanoylation.

Extent and Direction of Ghrelin Transport Across the Blood-Brain Barrier Is Determined by Its Unique Primary Structure

Writing Group: Professor P Armstrong (Imaging), Dr J Congleton,* Mr S W Fountain (Chairman),* Dr T Jagoe, Dr D F McAuley,* Dr J MacMahon,* Dr M F Muers,* Mr R D Page,* Dr P K Plant,* Dr M Roland, Dr R M Rudd, Mr W S Walker,* Dr T J Williams*. Specialist advisors: Professor M I Saunders (Royal College of Radiologists), Dr A G Nicholson (Royal College of Pathologists). *Members of the core Writing Group.

/pdf/guidelines-on-the-selection-of-patients-with-lung-cancer-3mztx2f3l5.pdf

Guidelines on the selection of patients with lung cancer forsurgery

The blood-brain barrier and immune function and dysfunction.

Although severe impairment on routine pulmonary function tests will identify patients with a high post-thoracotomy morbidity, cardiopulmonary complications often develop in patients with only a mild-to-moderate impairment in pulmonary function. To determine whether the preoperative exercise capacity can prospectively identify those at risk of developing complications, 22 patients scheduled for thoracotomy (mean age, 55.7 ± 2 yr) underwent an incremental exercise test on a cycle ergometer to determine their maximal O2 uptake prior to thoracotomy. Routine pulmonary function tests were performed and postoperative forced expiratory volume in one second (FEV1) was predicted from split function perfusion lung scan in all subjects. Eleven of the 22 patients had no cardiopulmonary complications postoperatively. The age, history of prior cardiovascular disease, degree of impairment on routine pulmonary function tests, and predicted postoperative FEV1 were similar in those who did and those who did not experience c...

Exercise capacity as a predictor of post-thoracotomy morbidity

https://journal.chestnet.org/article/S0012-3692(16)61719-1/pdf

Preoperative pulmonary function testing to predict postoperative morbidity and mortality

Prediction of Pulmonary Function Loss Due to Pneumonectomy Using 133Xe-Radiospirometry

Regional Functional Decrease in Bronchial Carcinoma

Disorders in the permeability of the cerebral vessels are probably an important pathogenetic factor in various diseases and pathological conditions. The ordinary anatomico-pathological examination of a brain does not disclose direct evidence of such a disturbance, but several morphological criteria may be produced in certain cases for such an assumption, e.g. a maximal distension and engorgement of the smaller veins and capillaries, signs of stasis, degenerative changes or complete necrosis of the vessel wall, distension of the perivascular spaces, often with serous fluid, petechial hemorrhages, and perivascular necrosis of the brain tissue. Scheinker recently described a number of pathological conditions displaying this histopathological picture and designated them “vasoparalysis” (1944, 1945, 1945). The ordinary technique applied to experimental animals to show the existence of a disturbance in the vascular permeability of the brain, cannot of course be employed agonally in man. When animal experiments revealed that, as far as special dye-stuffs are concerned, the cerebral vessels keep their permeability unchanged a short time post inortern, the way was open for experimental studies of human brains (Broman, 1938, 19-10). Such examinations were made and with positive results (Brornan, 1944, 1947). For example, a distinctly discernible passage of the dyes through the vascular walls into the cerebral tissue was demonstrated in different kinds of brain tumours, in regions of cerebral edema, in the plaques of multiple sclerosis, and perifocally around massive hemorrhages and softenings. The present investigation constitutes a continuation of the above studies. Earlier experience showed that the method is impaired by a number of considerable sources of error, and that several findings could not

Supravital analysis of disorders in the cerebrovascular permeability.

In earlier investigations colour indicators have shown that disorders in the cerebrovascular permeability are relatively brief. Broman (1940) , for example, showed that such a disorder was observable in the pial vessels only for about one hour after a 10-20 minute passage of air or fat emboli. With solid micro-embolism which become lodged in the vessels the disorder in the permeability localized in the immediate vicinity of the emboli lasted about five days (probably longer in cases with fat emboli in which the latter could be displaced later, e . g . by raising the blood pressure). Toxic lesions of the vascular wall such as the suspected allergic lesion produced experimentally in the brains of guinea-pigs by sheep hemolytic rabbit serum (Forssman, 1922, 1926; Skoog, 1937) lasted up to seven hours. (Broman k Lindberg-Broman, 1945). Another type of toxic vascular lesion produced by a certain contrast medium for cerebral angiograyhy (Umbradil for te) , was of an especially mild nature and disappeared already after one to two hours (Broman’ & OISSOR, 1948). The disseminated cerebrovascular disorder produced in insulin coma and metrazol shock ceased practically immediately aften the coma and the shock, respectively, had worn off (Rjerner, Broman & Swensson, 1944). In experiments with a disturbance of the cerebrovascular permeability due to local traumatization

Lawe Svanberg

Papers

Prediction of Pulmonary Function Loss Due to Pneumonectomy Using 133Xe-Radiospirometry

Regional Functional Decrease in Bronchial Carcinoma

Supravital analysis of disorders in the cerebrovascular permeability.

The duration of experimental disturbances in the cerebro‐vascular permeability due to circumscribed gross damage of the brain