Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085631 (agitation)
 12,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a 41-year-old male of citrullinemia associated with argininosuccinate acid synthetase deficiency. He was admitted to the Hitachi General Hospital because of finger tremor, restlessness and urinary incontinence. He had short stature and a poor appetite. Laboratory evaluation was summarized as follows: mild hypoglycemia, low plasma cortisol levels, delayed response of 17-OHCS and 17-KS to ACTH administration in urine, and delayed response of plasma ACTH level to insulin administration. In this case, ACTH deficiency is estimated to be a dysfunction of the hypothalamus. Replacement therapy of hydrocortisone improved his symptoms. He was readmitted to the hospital because of delirium and confusion, two weeks after the hydrocortisone administration. At that time, he had flapping tremor. Laboratory examination revealed hyperammonemia (NH3: 231 micrograms/dl) and mild elevation of GOT and GPT. Serum and urinary amino acid determination showed marked elevation of citrulline (478.1 nmol/ml in serum, 4681.2 mumol/day in urine). Lactulose administration, low protein diet and plasmapheresis were started, but he went into a coma. Without any improvement, he died on the 29th hospital day. Autopsy examination of the liver disclosed fatty change. Adrenal cortex depicted severe atrophy. Biochemical analysis of urea cycle enzymes of the liver and kidney showed decreased activity of argininosuccinate synthetase (liver: 0.0022 U/mg protein, 5% of that normal liver, kidney: 0.003 IU/mg protein, 20% of that in normal kidney). Citrullinemia associated with ACTH deficiency have not reported in the literature. It may be presumed that ACTH deficiency is concerned with the delayed onset of hyperammonemia. The relation between citrullinemia and endocrinological abnormalities is also discussed.
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PMID:[A case of citrullinemia associated with isolated ACTH deficiency, rapidly developing coma]. 133 25

Hypoglycaemia is possibly the most frequent metabolic emergency, in that insulin-induced hypoglycaemia is a common side-effect of treatment of a common disease. The symptoms are partly sympathetic and related to the release of catecholamines. These symptoms include sweating, tremor, palpitations, sensation of hunger, restlessness and anxiety. Other symptoms are caused by an insufficient supply of glucose to the brain, resulting in neuroglucopenia with symptoms like blurred vision, weakness, slurred speech, vertigo and difficulties in concentration. Symptom recognition is the primary and most effective defence against cerebral dysfunction which is the ultimate consequence of hypoglycaemia. Even in insulin-treated diabetic patients symptom failure might occur. Patients who experience severe episodes of hypoglycaemia do not constitute a special subgroup of patients. However, near-normalization of blood glucose levels have resulted in an increase in the incidence of severe hypoglycaemia. Moreover, the threshold for hormonal counter-regulatory responses in adrenaline, growth hormone and cortisol is lowered after a period of strict metabolic control in insulin-dependent diabetic patients. The glucose level at which the patients become subjectively aware of hypoglycaemia is correspondingly reduced. Other reasons for hypoglycaemia to occur are oral hypoglycaemic agents, especially sulfonylureas which may be potentiated by other drugs. Prolonged hypoglycaemia may be seen after first-order sulfonylureas, and may indicate glucose infusion as treatment. Next to insulin and sulfonylurea, ethanol is the most common cause of hypoglycaemia. In non-diabetics, hypoglycaemia will typically develop 6-24 h after a moderate or heavy intake of ethanol by a person who has had an insufficient intake of food for 1 or 2 days. Insulin-producing tumours, insulinomas and non-islet cell tumours may also be reasons for hypoglycaemia in non-diabetics. Treatment of mild episodes of hypoglycaemia is intake of fast-absorbing carbohydrates. Severe episodes can be treated with either i.v. dextrose or glucagon injected i.m. or i.v. The glycaemic response and recovery of a normal level of consciousness is 1-2 min slower after glucagon than after glucose.
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PMID:Endocrine emergencies. Hypoglycaemia. 173 95

The stability of protein-based pharmaceuticals (e.g., insulin) is important for their production, storage, and delivery. To gain an understanding of insulin's aggregation mechanism in aqueous solutions, the effects of agitation rate, interfacial interactions, and insulin concentration on the overall aggregation rate were examined. Ultraviolet absorption spectroscopy, high-performance liquid chromatography, and quasielastic light scattering analyses were used to monitor the aggregation reaction and identify intermediate species. The reaction proceeded in two stages; insulin stability was enhanced at higher concentration. Mathematical modeling of proposed kinetic schemes was employed to identify possible reaction pathways and to explain greater stability at higher insulin concentration.
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PMID:Kinetics of insulin aggregation in aqueous solutions upon agitation in the presence of hydrophobic surfaces. 194 48

Drugs that stimulate adrenergic receptors are expected to affect glucose and lipid metabolism. Therefore, it was deemed to be of interest to assess whether the new selective beta 2-adrenoceptor agonist, broxaterol, exerts any metabolic effect. Broxaterol has been evaluated in 21 patients, 18 men and 3 women, aged 34 to 80 years, with a diagnosis of reversible obstructive airways disease. Broxaterol was administered orally at doses of 0.5 mg thrice daily for 1-12 months, according to an open design. In addition to metabolic parameters (plasma glucose, insulin, high and low density lipoprotein-cholesterol, triglycerides, free fatty acids, glycerol, sodium, potassium), arterial pH, partial arterial oxygen and carbon dioxide pressure, lung function tests--forced expiratory volume in one second (FEV1), maximum mid-expiratory flow (MMEF75-25) and specific airways conductance (SGaw)--heart rate and blood pressure were assessed at baseline and after 1, 2, 3, 4, 5, 6, 9, 12 months of treatment. No statistically significant change from baseline was observed in the levels of plasma glucose, cholesterol, triglycerides, or free fatty acids. Plasma levels of insulin, glycerol and sodium only increased in the first three months of treatment; a slight hypokalaemia was also observed during the same period. The bronchodilation (significant increase in FEV1, MMEF75-25, SGaw) was maintained throughout the study; no hospital admission was necessary. Tremor, palpitations and restlessness were reported in six patients; no significant changes in heart rate and blood pressure were observed. The data suggest that the metabolic effects of long-term treatment with oral broxaterol can be considered as very negligible.
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PMID:Negligible metabolic effects of long-term oral treatment with a new beta 2-agonist: broxaterol. 198 79

The activity and Km of glucose transport of rat adipocytes are quite variable in the basal state. This could be due to differing levels of highly saturable transport against a background of less saturable transport. Such heterogeneity could lead to differing conclusions as to the Km of basal cells compared to insulin-stimulated cells depending on the choice of substrate, the range of concentrations tested, and the rigor of data analysis. In the present work, we used a cell preparation which was stable and partially activated by constant agitation. We used a two-component model to fit the concentration dependence of D-glucose uptake. We defined two parallel pathways of glucose entry, a high-affinity/low-capacity pathway and a low-affinity/high-capacity pathway. Both pathways were stereospecific and were inhibited by cytochalasin B. The low-affinity pathway in basal cells had 97% of the total capacity (Vmax) with a high Km (greater than 50 mM). A second pathway had a very low Km (less than 1 mM) and only 3% of the total capacity, but contributed to 30-60% of glucose uptake at 8 mM glucose. In insulin-stimulated cells, a pathway with a Km of 4-5 mM dominated and contributed 85% of glucose transport. The low-affinity but not the very high affinity pathway persisted in stimulated cells, but its contribution was only 10-15% of transport at 8 mM glucose. These results suggest the presence of at least two functionally distinct transporters whose respective contributions can be characterized by nonlinear regression of data over a wide range of glucose concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evidence for functionally distinct glucose transporters in basal and insulin-stimulated adipocytes. 268 69

Prolonged, gentle agitation of U100 insulin solutions containing various ingredients has shown that gelling can take place. The extent of gelling was evaluated by low shear rheometry and quantified in terms of the effective molecular weight increase using the method of reduced variables. Maximal viscosities of gelled systems in excess of 100 Pas were achieved. From a knowledge of the hydrodynamics of infusion pump systems, the reduction in insulin delivery rate caused by an increase in viscosity can be calculated. In commercial, syringe-driven pumps, pressure differentials as high as 10(4) Nm-2 and shear rates in excess of 10(4) s-1 can occur, although the flow is invariably laminar.
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PMID:Assessment of gelling in insulin solutions for infusion pumps. 286 10

The effect of insulin and factors which have insulin-like activity on the kinetic parameters of 3-O-methyl-D-glucose (MeGlc) transport in rat adipocytes were assessed. Carrier-mediated uptake of MeGlc was estimated by the difference in the amounts of [14C]MeGlc and L-[3H]glucose taken up in cells under equilibrium exchange conditions at 37 degrees C. The Km and Vmax values in basal cells were 17.4 mM and 0.24 nmol/10(6) cells/s, respectively. Removal of endogenous adenosine by adenosine deaminase resulted in a 26% decrease in the basal rate due to a slight increase in the Km (19.6 mM) and a decrease in the Vmax value (0.20 nmol/10(6) cells/s). The maximum concentration (10 nM) of insulin decreased the Km to approximately one-half of the basal (7.1 mM) concomitant with an 8.5-fold increase in the Vmax value (2.04 nmol/10(6) cells/s). Submaximal concentrations (50 and 150 pM) of insulin, N6-phenylisopropyladenosine (1 microM), mechanical agitation of cells by centrifugal force (160 x g), low temperature (15 degrees C), 12-O-tetradecanoylphorbol-13-acetate (1 microM), and hydrogen peroxide (10 mM) all decreased the basal Km value to a range of 13.5-7.3 mM, concomitant with a 1.7-7.4-fold increase in the Vmax. A possible explanation for the alterations in the kinetic parameters may be that insulin and other factors cause the translocation of the mobile low-Km glucose transporters from an intracellular site to the cell surface, where the stationary high-Km transporters are located. Thus, when the Km and Vmax values of the hypothetical high-Km transporters were assumed to be 20 mM and 0.20 nmol/10(6) cells/s, respectively, and the Km of the low-Km transporters was assumed to be 7 mM, the theoretical Km decreased from 20 to 7.5 mM as the Vmax of the low-Km transporters increased from near 0 to 2.0 nmol/10(6) cells/s. The relation between empirical Km and Vmax values as affected by several agents and conditions followed closely the relation predicted by the above two-transporter model.
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PMID:Reassessment of the translocation hypothesis by kinetic studies on hexose transport in isolated rat adipocytes. 304 14

The stability of a new insulin formulation (lyophilized U100 insulin, Organon) was investigated in vitro in conditions reproducing those of in vivo implanted devices, i.e., constant horizontal agitation at 37 degrees C for 4 wk in various containers and 8 wk in different solvents. Physical stability was assessed by ultraviolet absorption, chemical stability by HPLC, and biological stability by hypoglycemia tests in mice. Insulin precipitated in glass vials but remained clear and active in polyethylene reservoirs and after passage through catheter and pumps in motion, although only 83-90% of insulin was delivered chemically intact. In acidic solvent, insulin showed a major gradual transformation into deamidized derivatives (up to 78% after 8 wk), although still fully active and clear, as expected from previously published excellent in vivo results with acidic insulins. Heparin addition to neutral insulin solution (500 IU/ml) did not alter the properties of the two compounds and might thus be tried to prevent in vivo catheter obstruction due to fibrin deposition.
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PMID:Stable insulin for implantable delivery systems: in vitro studies with different containers and solvents. 329 79

We have previously described experimental conditions where basal methylglucose transport in adipocytes exhibited an apparent Km of approximately 35 mM. Under those conditions insulin stimulated transport predominantly by decreasing the transport Km (Whitesell, R. R., and Abumrad, N. A. (1985) J. Biol. Chem. 260, 2894-2899). Our findings were in contrast with earlier reports that the Km of basal glucose transport was low (3-5 mM) and similar to that of transport in insulin-treated cells. In this study we have investigated the effect of different experimental conditions on the kinetics of basal glucose transport in adipocytes. When transport was assayed at 37 degrees C, cell agitation for 10 min prior to the transport assay decreased the basal Km from 35 to 12 mM. Deprivation of metabolic substrate produced a further reduction down to 2 mM. Refeeding starved cells with 1 mM glucose returned the Km back up to 12 mM in agitated cells and to 40 mM in stabilized cells. The effects of agitation to lower and of glucose to raise the basal Km were prevented by preincubating cells with dinitrophenol. Cell agitation or substrate lack did not alter the Vmax of basal transport and were without effect on both Km and Vmax in insulin-treated cells. The temperature dependencies of the kinetics of basal and stimulated transport were studied. A decrease in the assay temperature from 37 to 23 degrees C caused both basal Km and Vmax to drop proportionately from 25 to 5 mM, and 13 to 3.6 nmol/(microliter X min), respectively. In insulin-stimulated cells, only the Vmax was decreased (Km went from 3.5 to 3 mM, Vmax from 45 to 17 nmol/(microliter X min]. The results support the concept that experimental conditions can produce large changes in the Km of basal glucose transporters. Furthermore they explain why, under certain assay conditions (with temperatures around 23 degrees C or with deprivation of metabolic substrate), the effect of insulin on transport Km is not observed. Our data also suggest that basal transport characteristics do not persist in insulin-treated cells. We would propose that one of the actions of insulin (in addition to raising Vmax) is to change the characteristics of basal transporters by overriding metabolic factors which keep the Km high. Alternatively, insulin could cause the disappearance of basal transporters as new and different ones are recruited from intracellular stores.
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PMID:Modulation of basal glucose transporter Km in the adipocyte by insulin and other factors. 353 34

The levels of insulin-like growth factors 1 and 2 (IGF-1 and IGF-2) and somatomedin B in serum and cerebrospinal fluid (CSF) were investigated in alcoholic patients for 4 weeks after alcohol intake stopped. Throughout the observation period, CSF levels of IGF-2 were significantly decreased compared to those of healthy controls, whereas CSF levels of somatomedin B increased significantly 8 days after alcohol withdrawal and remained elevated throughout the observation period. CSF levels of IGF-2 were significantly correlated to measurements of ventricular enlargement on computed tomography. Somatomedin B levels were significantly correlated to clinical variables such as pulse, temperature, and agitation. No increase in the serum levels of somatomedin B were observed, but an increase in serum IGF levels was found in the patient group.
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PMID:Circulating levels of insulin-like growth factors 1 and 2 and somatomedin B in alcoholic patients. 374 91


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