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PubMed1979

[Sympathetic-adrenal and enterochromaffin systems and homeostatic indices in open-heart surgical operations under morphine anesthesia].

Catecholamine, serotonin and histamine metabolism and the level of acid metabolites and the activity of the enzymes lactate dehydrogenase and catalse in blood were studied in patients with congenital heart disease who were operated on under conditions of extracorporeal circulation and morphine anesthesia. The results obtained were compared with the values of acid-base balance, haemodynamics and volume of diuresis. It wwas found that the period of morphine induction was marked by a significant increase in the blood plasma noradrenalin content in the absence of essential changes in the other biochemical and hemodynamic indices studied. No significant changes were noted in the systems of neurohumoral and tissue regulation, indices of the redox processes and renal excretion in the most traumatic periods of the operation. The data obtained allow morphine to be accepted as an anesthetic which provides adequate protection of the organism from operative trauma.

Adolescent↗

PubMed1989

Malignant paraganglioma of the organ of Zuckerkandl. Initially diagnosed as renal cell carcinoma by biopsy of a right humeral fracture lesion.

Malignant paraganglioma of the organ of Zuckerkandl (malignant POZ) in a 38-year-old woman is reported. Ten months before her death, the patient suffered from right shoulder pain. By biopsy of a pathological right humeral fracture, a histological diagnosis of metastatic renal cell carcinoma was initially made. However, autopsy revealed a left retroperitoneal tumor, which was diagnosed as malignant POZ. Upon immunohistochemical examination, tumor cells showed definite positivity for neuronspecific enolase (NSE) and chromogranins, and neurosecretory granules were found electron microscopically. The skeletal system is the most common site for distant metastases of malignant POZ. We were unable to find any previous reports of malignant POZ which were first manifested as humeral metastases, as in the present case. As paraganglioma might be histologically confused with a large variety of neoplasms (e.g. renal cell carcinoma), differential diagnosis of this condition is discussed.

Adult↗

PubMed1992

Survival and integration of bovine chromaffin cells transplanted into rat central nervous system without exogenous trophic factors.

Our previous studies have demonstrated that suspension grafts of isolated bovine chromaffin cells survive in the periaqueductal gray (PAG) of rat midbrain for up to 1 year after transplantation. The current study aimed to determine whether this type of graft could survive transplantation into sites other than the PAG that can benefit from chromaffin cell secretory products. In this study, electron microscope analysis showed that chromaffin cells implanted into the frontal neocortex, striatum, PAG, or the subarachnoid space overlying the spinal cord survived for at least 8 weeks without evidence of degeneration. Intraparenchymally placed grafts appeared relatively avascular and well integrated within the host parenchyma. When blood vessels were found, they were primarily at the host-graft border and were of the nonfenestrated central nervous system (CNS) type. Numerous synapses were present between the grafted cells and host neuronal processes. In addition, extensive intercommunication, via gap junction-like structures, was common in the grafts. Morphologic evidence of granular secretion was most commonly seen in striatal grafts. In contrast, subarachnoid grafts displayed minimal interaction with the host spinal tissue and were heavily vascularized with fenestrated capillaries. Despite morphologic differences between intra- and extraparenchymal grafts, this study demonstrates that isolated suspensions of bovine chromaffin cells survive transplantation into CNS sites without exogenous trophic factors and suggests that these cells are potential candidates for neural transplantation into these regions.

Animals↗

PubMed1992

The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release.

MDMA ("ecstasy") has been widely reported as a drug of abuse and as a neurotoxin. This report describes the mechanism of MDMA action at serotonin transporters from plasma membranes and secretory vesicles. MDMA stimulates serotonin efflux from both types of membrane vesicle. In plasma membrane vesicles isolated from human platelets, MDMA inhibits serotonin transport and [3H]imipramine binding by direct interaction with the Na(+)-dependent serotonin transporter. MDMA stimulates radiolabel efflux from plasma membrane vesicles preloaded with [3H]serotonin in a stereo-specific, Na(+)-dependent, and imipramine-sensitive manner characteristic of transporter-mediated exchange. In membrane vesicles isolated from bovine adrenal chromaffin granules, which contain the vesicular biogenic amine transporter, MDMA inhibits ATP-dependent [3H]serotonin accumulation and stimulates efflux of previously accumulated [3H]serotonin. Stimulation of vesicular [3H]serotonin efflux is due to dissipation of the transmembrane pH difference generated by ATP hydrolysis and to direct interaction with the vesicular amine transporter.

3,4-Methylenedioxyamphetamine↗

PubMed1984

Hyperplasia of antral G cells in uraemic patients.

In this study we have performed a quantitative analysis of antral gastrin cells in 9 uraemic patients under dialytic treatment compared to a group of 10 chronic gastritis patients with a similar histological degree of gastritis. Immunocytochemistry was carried out on endoscopic biopsies of both groups. Using a computerised image analysing system we showed a significant increase of G-cell density (number of cells/mm2) in uraemic patients compared to non-uraemics (p less than 0.001). These findings provide a further morphological basis for the elevation of gastrin levels in chronic uraemic patients, suggesting the existence of a specific factor inducing G-cell proliferation in these patients.

Adult↗

PubMed1985

[Enteroendocrine cells, their structure and function].

The modern classification of the gastroenteropancreatic endocrine system (GEPES) is presented. Qualitative and quantitative composition of the entero-endocrine system (EES) included in the GEPES is considered, as well as functional role of every type of the cells. The literature data are summarized and the morphology at the light optic and electron microscopic levels of the endocrine cells and the peptidergic nerves of the intestine is demonstrated. The existing methods for investigation of the EES endocrine cells and for the whole neuroendocrine complex of the gastro-intestinal tract taken together are analysed.

APUD Cells↗

PubMed1991

Physiological disturbances in hypoglycaemia: effect on subjective awareness.

Deficiencies in the release of glucagon and adrenaline during hypoglycaemia in diabetic patients are associated with a high frequency of severe hypoglycaemic episodes. These have been attributed to a resulting inability to increase hepatic glucose output acutely. A more important consequence may be reduced awareness of impending hypoglycaemia. Such hypoglycaemia unawareness is related to, but not entirely explained by, diminished sympathetic activity, perhaps due to failure to activate the sympathoadrenal system until a lower blood glucose level is achieved. The patient's subsequent failure to act appropriately would then be due to impaired cerebral function preventing the perception of sympathoadrenal activation during the more severe hypoglycaemia. Unawareness of moderate hypoglycaemia is common in diabetic patients. Autonomic neuropathy probably accounts for only a few cases of hypoglycaemia unawareness and other factors which are potentially important include duration of diabetes, glycaemic control, insulin species, and the degree and frequency of hypoglycaemia. Further research is required to discover both the pathophysiological mechanisms of, and the treatment needed to reverse or prevent, the abnormality.

Awareness↗

PubMed2005

Purification and characterization of bovine adrenal cytochrome b561 expressed in insect and yeast cell systems.

Bovine adrenal chromaffin granule cytochrome (cyt) b561 is a transmembrane hemoprotein that plays a key role in transporting reducing equivalents from ascorbate to dopamine-beta-hydroxylase for catecholamine synthesis. We have developed procedures for expression and purification of functional bovine adrenal cyt b561 in insect and yeast cell systems. The bovine cyt b561 coding sequence, with or without a hexahistidine-tag sequence at the C-terminus, was cloned into the pVL1392 transfer vector under the control of the polyhedrin promoter to generate recombinant baculovirus for protein expression in Sf9 insect cells (approximately 0.5 mg detergent-solubilized cyt b561/L culture). For the yeast system, the cyt b561 cDNA was modified with a hexahistidine-tag sequence at the C-terminus, and inserted into the pPICZB vector under the control of the alcohol oxidase promoter. The recombinant plasmid was transformed into Pichia pastoris GS115 competent cells to give methanol-inducible cyt b561 expression (approximately 0.7 mg detergent-solubilized cyt b561/L culture). Recombinant His-tagged cyt b561 expressed in Sf9 or Pichia cells was readily solubilized from membrane fractions with dodecyl maltoside and purified to electrophoretic homogeneity by one-step chromatography on Ni-NTA affinity resin. The purified recombinant cytochrome from both systems had a heme to protein ratio close to two and was fully functional, as judged by comparison with the spectroscopic and kinetic parameters of the endogenous cytochrome from chromaffin granules. A novel procedure for isolation of chromaffin granule membranes was developed to utilize frozen adrenal glands instead of fresh tissue.

Adrenal Glands↗

PubMedDate not supplied

[Effect of chemical destruction of hypothalamic monoaminergic terminals on function of the adrenal cortex, thyroid gland and enterochromaffin system].

In experiments on rats the influence of noradrenergic, dopaminergic terminal destruction after 6-hydroxydopamine intraventricular injection and of serotoninergic terminal damage following 5,6-hydroxytryptamine administration on the adrenal cortex, thyroid and enterochromaffin body function was studied under basal conditions and during cold stress. As a result of noradrenergic terminal destruction basal- and cold stress-induced functional activity of the adrenal cortex and enterochromaffin body augmented. After serotoninergic terminal damage stress-induced intensification of the functional activity of the endocrine glands mentioned was blocked. The thyroid gland function changed under the hypothalamic noradrenergic and serotoninergic terminal destruction. In the first case a cold-induced rise in the gland functional activity was blocked and in the second one a stress-provoked growth of the thyroid gland activity was rather more than in the control.

Adrenal Cortex↗

PubMed1986

Glucoregulation during exercise: hypoglycemia is prevented by redundant glucoregulatory systems, sympathochromaffin activation, and changes in islet hormone secretion.

During mild or moderate nonexhausting exercise, glucose utilization increases sharply but is normally matched by increased glucose production such that hypoglycemia does not occur. To test the hypothesis that redundant glucoregulatory systems including sympathochromaffin activation and changes in pancreatic islet hormone secretion underlie this precise matching, eight young adults exercised at 55-60% of maximal oxygen consumption for 60 min on separate occasions under four conditions: (a) control study (saline infusion); (b) islet clamp study (insulin and glucagon held constant by somatostatin infusion with glucagon and insulin replacement at fixed rates before, during and after exercise with insulin doses determined individually and shown to produce normal and stable plasma glucose concentrations prior to each study); (c) adrenergic blockage study (infusions of the alpha- and beta-adrenergic antagonists phentolamine and propranolol); (d) adrenergic blockade plus islet clamp study. Glucose production matched increased glucose utilization during exercise in the control study and plasma glucose did not fall (92 +/- 1 mg/dl at base line, 90 +/- 2 mg/dl at the end of exercise). Plasma glucose also did not fall during exercise when changes in insulin and glucagon were prevented in the islet clamp study. In the adrenergic blockade study, plasma glucose declined initially during exercise because of a greater initial increase in glucose utilization, then plateaued with an end-exercise value of 74 +/- 3 mg/dl (P less than 0.01 vs. control). In contrast, in the adrenergic blockade plus islet clamp study, exercise was associated with glucose production substantially lower than control and plasma glucose fell progressively to 58 +/- 7 mg/dl (P less than 0.001); end-exercise plasma glucose concentrations ranged from 34 to 72 mg/dl. Thus, we conclude that: (a) redundant glucoregulatory systems are involved in the precise matching of increased glucose utilization and glucose production that normally prevents hypoglycemia during moderate exercise in humans. (b) Sympathochromaffin activation, perhaps sympathetic neural norepinephrine release, plays a primary glucoregulatory role by limiting glucose utilization as well as stimulating glucose production. (c) Changes in pancreatic islet hormone secretion (decrements in insulin, increments in glucagon, or both) are not normally critical but become critical when catecholamine action is deficient. (d) Glucoregulation fails, and hypoglycemia can develop, both when catecholamine action is deficient and when changes in islet hormones do not occur during exercise in humans.

3-Hydroxybutyric Acid↗

PubMed1993

Unaltered cerebral blood flow during hypoglycemic activation of the sympathochromaffin system in humans.

To determine if increases in plasma epinephrine and norepinephrine caused by hypoglycemia are associated with increments in cerebral blood flow (CBF), we measured CBF with positron emission tomography in normal humans at ambient fasting arterial plasma glucose levels and at clamped plasma glucose levels of 5.3, 3.5, and 2.8 mmol/l using the hyperinsulinemic, stepped hypoglycemic clamp technique. Despite significant increases in plasma epinephrine to 7,340 +/- 350 (SE) pmol/l and in plasma norepinephrine to 3.32 +/- 0.35 nmol/l, mean hemispheric CBF (41 +/- 1, 49 +/- 1, 48 +/- 2, and 51 +/- 3 ml x 100 g-1 x min-1) remained constant at the ambient (5.2), 5.3, 3.5, and 2.8 mmol/l glycemic levels, respectively. Furthermore, there was no correlation between CBF and either plasma epinephrine levels ranging from 160 to 10,580 pmol/l or plasma norepinephrine levels ranging from 0.56 to 5.10 nmol/l. Failure to demonstrate any dose-response relationship between plasma catecholamine levels and CBF argues against their primary role in cerebrovascular control during hypoglycemia.

Adult↗

PubMed1977

[Pathomorphologic studies of the endocrine cells in the gastrointestinal mucosa. Physiology, cytochemistry and ultrastructure (author's transl].

With combined immunofluorescent, cytochemical and electron microscopic investigations the enterochromaffin cell system has been differentiated into 5 distinct endocrine cell types in the human stomach and into 8 cell types in the intestine. These endocrine cells are probably of neuroectodermal origin and belong to the APUD (amine precursor uptake and decarboxylation)-system. Maximal gastrointestinal hormone concentrations as determined by tissue extracts correlate fairly well to the location of each endocrine cell type in various segments of the gastrointestinal tract. In certain gastroenteropathies the pathophysiological disturbances can be explained by pathomorphological alterations of the disseminated endocrine cells. 1. The gastrin-producing G-cell is the predominating endocrine cell in the gastric antrum. Besides immunocytochemistry the G-cell can be demonstrated with argyrophilic reaction (Grimelius, 1968), masked metachromasia and leadhematoxylin. The ultrastructural features are variable, depending on functional activity. The secretory granules are usually only slightly osmiophilic, measuring 200 till 250 nm in diameter. By some working groups a positive immunofluorescence with gastrin-antisera has been demonstrated in A1- or D-cells of the pancreatic islets. However, numerous negative results have been reported, too. Considering physiological conditions, a gastrin-secretion of the human pancreatic islets has not been secured without doubt. 2. The EC-cell produces serotonin and in the intestine motilin, too. Besides the formaldehyde-induced fluorescence, these cells can be demonstrated with diazonium and argentaffin reactions, less specific with argyrophilic methods. Ultrastructurally the EC-granules are easily differeniated from the other endocrine cells by their pronounced osmiophilia and pleomorphism. In experimental conditions the EC-cells demonstrate species- and site-specific alterations. With reserpine no ultrastructural changes were demonstrable in EC-cells of the rat. However, marked ultrastructural alterations with an increase of the hormone-producing organelle system were noticed after administration of parachlorophenylalanine (PCPA) which interferes with serotonine synthesis; 5. The gastric D-cells are characterized by large secretory granules similar to pancreatic D-cells. They secrete the HCl-inhibitory peptide somatostatin. 4. The D1-cell is a cell type with unknown function. The cytoplasm contains small granules with variable electron density. According to most authors, they represent a distinct cell type and not just a variant of the G-cells. It may be very difficult, however, to separate certain forms of D1-cells from functionally altered G-cells. 5. The A-cell can be found in the gastric mucosa of certain animal species, where it has been demonstrated by immunocytochemistry with antisera to gut-glucagon. This cell type does not occur in the human gastric mucosa. 6...

Adenoma, Islet Cell↗

PubMed1988

Enterochromaffin (EC-) cells of the mammalian gastro-entero-pancreatic (GEP) endocrine system: cellular source of pro-dynorphin-derived peptides.

It has long been disputed whether mammalian enterochromaffin (EC-) cells contain a peptide in addition to serotonin. Previous immunohistochemical studies have provided evidence for the presence of enkephalins in EC-cells. These findings, however, are equivocal. Therefore, the problem of opioid peptides in EC-cells has been re-examined in the gastro-intestinal mucosa of dog, guinea-pig and man. A battery of antisera against derivatives of pro-opiomelanocortin, pro-enkephalin and pro-dynorphin have been applied to semithin serial sections of the tissues, in combination with fluorescence histochemistry and serotonin immunocytochemistry. Our findings indicate that EC-cells of the investigated species contain pro-dynorphin-related peptides, i.e. dynorphin A and alpha-neo-endorphin, but no derivatives from pro-opiomelanocortin or pro-enkephalin. Since remarkable interspecies variations occur with respect to the number and staining characteristics of opioid immunoreactive EC-cells, it is concluded that pro-dynorphin shows specific routes of post-translational processing depending upon the species and the gastro-intestinal segment investigated. Future studies should focus on the mutual relationships between serotonin and dynorphins and on the physiological significance of these peptides in the gastrointestinal tract.

Adrenal Medulla↗

PubMed1998

Forearm norepinephrine spillover during standing, hyperinsulinemia, and hypoglycemia.

Plasma norepinephrine (NE) concentrations are a fallible index of sympathetic neural activity because circulating NE can be derived from sympathetic nerves, the adrenal medullas, or both and because of regional differences in sympathetic neural activity. We used isotope dilution measurements of systemic and forearm NE spillover rates (SNESO and FNESO, respectively) to study the sympathochromaffin system during prolonged standing, hyperinsulinemic euglycemia, and hyperinsulinemic hypoglycemia in healthy humans. Prolonged standing led to decrements in blood pressure without increments in heart rate, the pattern of incipient vasodepressor syncope. FNESO was not increased (0.58 +/- 0.20 to 0. 50 +/- 0.21 pmol. min-1. 100 ml tissue-1), suggesting that the approximately twofold increments in plasma NE and SNESO were derived from sympathetic nerves other than those in the forearm (with a possible contribution from the adrenal medullas). Hyperinsulinemia per se (euglycemia maintained) stimulated sympathetic neural activity, as evidenced by increments in FNESO (0.57 +/- 0.11 to 1.25 +/- 0.25 pmol. min-1. 100 ml tissue-1, P < 0.05), but not adrenomedullary activity. Hypoglycemia per se stimulated adrenomedullary activity (plasma epinephrine from 190 +/- 70 to 1720 +/- 320, pmol/l, P < 0.01). Although SNESO (P < 0.05) and perhaps plasma NE (P < 0.06) were raised to a greater extent during hyperinsulinemic hypoglycemia than during hyperinsulinemic euglycemia, FNESO was not. Thus these data do not provide direct support for the concept that hypoglycemia per se also stimulates sympathetic neural activity.

Adult↗

PubMed1998

[Nerve growth factor and diabetic neuropathy].

INTRODUCTION: The progress made by contemporary neurobiology opens new horizons both for study and for treatment of disorders of the nervous system. At the present time we are in the age of growth factors. These are molecules which affect survival, development and the normal functioning of cell populations. DEVELOPMENT: One of the most widely studied growth factors is nervous growth factor (NGF) which is necessary for normal life of various types of neurones, including sensory nerves and nerves derived from the neural crests. Diabetic neuropathy, worldwide a major neurological disorder, is primarily characterized by involvement of the fine fibres for temperature and pain perception and also by a variety of autonomic disorders. The great dependence of sensory and sympathetic nerves on NGF, the quantity of results which show alterations in the levels of neurotrophic factors in diabetic neuropathy (DN), and the encouraging experimental and clinical results of using NGF as a new alternative to treatment with DN, were the basic reasons which led us to do this study. CONCLUSIONS: We started by considering neurotrophic factors, especially NGF and its connection with DN disorders and its clinical applications, we made a summary of the main findings in this field to date.

Alzheimer Disease↗

PubMed1996

Microelectrodes for the measurement of catecholamines in biological systems.

Many of the molecules involved in biological signaling processes are easily oxidized and have been monitored by electrochemical methods. Temporal response, spatial considerations, and sensitivity of the electrodes must be optimized for the specific biological application. To monitor exocytosis from single cells in culture, constant potential amperometry offers the best temporal resolution, and a low-noise picoammeter improves the detection limits. Smaller electrodes, with 1-micron diameters, provided spatial resolution sufficient to identify the locations of release sites on the surface of single cells. For the study of neurotransmitter release in vivo, larger cylindrical microelectrodes are advantageous because the secreted molecules come from multiple terminals near the electrode, and the greater amounts lead to a larger signal that emerges from the Johnson noise of the current amplifier. With this approach, dopamine release elicited by two electrical stimulus pulses at 10 Hz was detected with fastscan cyclic voltammetry in vivo. Nafion-coated elliptical electrodes have previously been shown to be incapable of detecting such concentration changes without extensive signal averaging. In addition, we demonstrate that high-pass filtering (200 Hz) of cyclic voltammograms recorded at 300 V/s decreases the background current and digitization noise at these microelectrodes, leading to an improved signal. Also, high-pass filtering discriminated against ascorbic acid, DOPAC, and acidic pH changes, three common interferences in vivo.

Animals↗

PubMed1996

Hormonal and metabolic adjustments during exercise in hypoxia or normoxia in highland natives.

In sea-level natives, exposure to hypoxia for a few weeks is characterized by an increased dependence on blood glucose and a decreased reliance on lactate for energy metabolism during exercise. These metabolic adjustments have been attributed to behavioral changes in the sympathoadrenergic and pancreatic systems. The aim of this study was to test the hypothesis of a reduced sympathoadrenergic activation and subsequent metabolic changes when high-altitude natives are acutely exposed to normoxia. Young Andean natives performed incremental exercise to exhaustion during hypoxia (arterial PO2 55.1 +/- 1.1 Torr) or during acute normoxia (arterial PO2 78.7 +/- 1.7 Torr). As a whole, oxygen uptake was increased in normoxia compared with hypoxia during graded exercise. This finding is not related to a decrease in anaerobic metabolism but rather is interpreted as a consequence of a shift in substrate utilization during exercise (increased contribution of fat as assessed by a reduction in the respiratory exchange ratio). These metabolic changes are not accompanied by modifications of glucoregulatory hormones (catecholamines, insulin, and glucagon). In particular, the exercise-induced catecholamine secretion was similar in chronic hypoxia and acute normoxia. As a consequence, blood lactate accumulation during incremental exercise was similar in both conditions. It is concluded that high-altitude natives do not display any sign of a greater sympathoadrenergic activation during chronic hypoxia and that the exercise-induced hormonal changes remained unaffected by acute inhalation of a normoxic gas mixture.

Adult↗

PubMed1976

[Distribution of the enterochromaffin ("EC") cells and those of the "APUD" series in the gastrointestinal tract of ruminants].

The research was carried out on the vorestomachs, abomasum and on the various tracts of gut of adult Cattle, Sheep and Goat, because Ruminants, not previously studied with respect to this problem, have, as is well known, particular morpho-functional characteristics of the digestive system. The results can be synthetized as follows: 1) either "EC" (5-HT-producing) or "APUD" cells (peptide hormones-producing) are not demonstrable in the vorestomachs. 2) "EC" cells are present in the various areas of abomasum (particularly numerous in the fundus glands) and in the different tracts of the gut (predominantly in the duodenum and in the rectum). 3) In the "APUD" cells of the abomasum gastrin-producing "G" cells are certainly demonstrable. They are present only in the pyloric glands, where they prevail in the middle third. Only in the cattle, cells which have all the histochemical characteristics of "G" cells, but are quite morphologically different, are also present in the same area. An interesting peculiarity seems to be the reduced number of "APUD" cells, compared with that of Monogastrics: it was impossible, in fact, to demonstrate some cells ("A", "A-like","X", "D", "D1", "ECL") which are described by other Authors in the stomach of various Mammals. 4) In the small intestine, endocrine cells, probably heterogenous are present, resulting more numerous in the duodenum. 5) In the coecum, colon and rectum, cells comparable to enteroglucagon-producing "EG" cells, are present; they are particularly numerous in the rectum, where cells similar to "H" cells are also present.

Abomasum↗