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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The molecular mechanisms for general anesthesia are probably restricted to a sensitive set of target sites in the brain. Membrane hyperpolarization, brought about by increased potassium channel conductance, is coupled to opiate mu receptors, to alpha 2- adrenoceptors, and to muscarinic M2 receptors, all of which have anesthetic-sparing effects. One type of potassium channel, the ATP-sensitive potassium channel (IKATP) has well-known agonists: cromakalim and pinacidil. The effects on isoflurane minimum alveolar concentration (MAC) of intracerebroventricular injection of these IKATP agonists and of the alpha 2-adrenoceptor agonist clonidine were studied in rats. Baseline MAC was 1.60% (+/- 0.02 SEM) isoflurane in oxygen. 10 micrograms clonidine decreased MAC by 42% of baseline (P less than 0.05); 20 micrograms clonidine decreased MAC by 58% of baseline (P less than 0.01). Neither cromakalim (20 micrograms) nor pinacidil (20 micrograms) had any effect on MAC. The results imply that neither indiscriminate agonist action of volatile anesthetics at potassium channels nor indiscriminate inhibitory membrane hyperpolarization is likely to be a fundamental mechanism of anesthesia. Furthermore, potassium channels coupled to opiate mu receptors, to alpha 2 adrenoceptors, and to muscarinic M2 receptors are probably not the IKATP type.
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PMID:ATP-sensitive potassium channel agonists do not alter MAC for isoflurane in rats. 155 Feb 81

Six patients (21-50 years) with growth hormone deficiency and panhypopituitarism were given recombinant growth hormone, somatotropin, 0.04-0.1 U.kg.body wt-1.day-1, for 12 months. All patients reported improved well-being with increased working capacity. Bone mineral density, as measured by single photon absorptiometry at two sites on the forearm, showed increased values in 5/6 patients after 12 months when measured at the most distal site (predominantly trabecular bone) and in 4/6 at the more proximal site (predominantly cortical bone). Five patients continued therapy for an additional year and after 18 months a significant increase in bone mineral density was seen at both the distal and proximal sites. The mean annual increase in bone mineral density was 12.0 +/- 0.6 (SEM)% and 3.8 +/- 1.3% at the distal and proximal sites, respectively. In a growth hormone deficient control group without growth hormone therapy, the corresponding values were -2.4 +/- 0.6% and -1.9 +/- 0.4%, respectively. Lean body mass, estimated anthropometrically, increased significantly after 12 months and total body potassium, measured by whole body counting technique, increased in 4/6 patients. During growth hormone treatment, the IGF-1 values were above the mean values for age and 50% of the values were above the mean +2 SD. B-glucose, P-insulin, serum IGF-2, procollagen-III peptide and phosphate increased and urea, creatinine and IGF-binding protein-1 decreased during treatment. The beneficial effects of growth hormone substitution, especially on bone mineral density, indicate that growth hormone substitution should be considered in all patients with hypopituitarism and growth hormone deficiency, irrespective of age.
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PMID:Potent effect of recombinant growth hormone on bone mineral density and body composition in adults with panhypopituitarism. 162 80

Plasma renin activity (PRA), urinary excretions of PGE2, 6-keto-PGF1 alpha (6KPGF), TXB2 and renal function were determined in healthy women both in normal potassium balance (N, n = 14) and in experimental potassium depletion (KD). KD was induced by natriuretic treatment--associated to replacement of net NaCl and water losses--in the presence of either normal (congruent to 50 mmol/d) or low (less than or equal to 10 mmol/d) dietary potassium intake. By using different depletive patterns, three groups with estimated cumulative potassium deficit (mean +/- SEM) of 124 +/- 38 (KD0, n = 8), 160 +/- 43 (KD1, n = 8) and 198 +/- 22 mmol (KD2, n = 6), respectively, were obtained. Renal function by the clearance (cl.) method and urinary prostanoid concentrations by the RIA method were estimated during hypotonic polyuria (oral water load) and subsequent moderate antidiuresis induced by a low-dose infusion of lysine-8-vasopressin. 1. In KD0 group the potassium depletive treatment was inefficacious in significantly reducing either the plasma potassium concentration (PK) or the urinary potassium excretion (UKV). The reductions of PK and UKV as well as the enhancement of PRA became significant in KD1 and KD2 groups. 2. The urinary prostanoid excretions were not significantly changed in the KD0 and KD1 groups while in the KD2 group they were reduced, mainly concerning the urinary 6KPGF excretion. 3. Furthermore in the KD2 group, with larger potassium depletion, some of the typical hypokalemic renal dysfunctions appeared. The data suggest that a pathophysiologically critical degree of potassium depletion is associated with an inhibited renal prostanoid synthesis as well as an increased renin secretion.
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PMID:Urinary prostanoid excretion in healthy women with different degrees of induced potassium depletion. 163 Nov 74

During lung transplantation, a number of factors may cause endothelial injury to the donor organ, including ischemia, inadequate preservation, cardiopulmonary bypass, high potassium concentrations, and reperfusion. In this study, protein accumulation index (PAI) was used to assess pulmonary endothelial permeability (PEP) in ten patients immediately after lung transplantation. Six were studied sequentially every other day for ten days postoperatively. The PAI was also measured using the same technique in a group of 11 normal volunteers. Mean PAI x 10(-3)/min +/- (SEM) for ten patients measured within 36 h of transplantation was 1.27 (0.56) compared with 0.45 (0.08) for the normal group (p = 0.09). No correlation was found between preservation time and PAI following reperfusion. Three episodes of lung rejection were observed in two patients during the first ten postoperative days, during which PAI rose to 2.26 (0.26) compared with 0.73 (0.11) for all other studies in the group (p less than 0.01). We conclude that no increase in PEP could be demonstrated after graft reperfusion following lung transplantation as assessed by PAI in this small group of patients. However, further studies may show the technique to be useful in the detection of subsequent episodes of graft rejection.
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PMID:Pulmonary endothelial permeability following lung transplantation. 164 25

Serum potassium, aldosterone and insulin, and plasma adrenaline, noradrenaline and cyclic adenosine 3':5'-monophosphate (cAMP) concentrations were measured during graded exhausting exercise and during the following 30 min recovery period in six untrained young men. During exercise there was an increase in concentration of serum potassium (4.74 mmol.l-1, SEM 0.12 at the end of exercise vs 3.80 mmol.l-1, SEM 0.05 basal, P less than 0.001), plasma adrenaline (2.14 nmol.l-1, SEM 0.05 at the end of exercise vs 0.30 nmol.l-1, SEM 0.02 basal, P less than 0.001), plasma noradrenaline (1.10 nmol.l-1, SEM 0.64 at the end of exercise vs 1.50 nmol.l-1, SEM 0.05 basal, P less than 0.001), serum aldosterone (0.92 nmol.l-1, SEM 0.14 at the end of exercise vs 0.36 nmol.l-1, SEM 0.05 basal, P less than 0.01), and plasma cAMP (35.4 nmol.l-1, SEM 2.3 at the end of exercise vs 21.4 nmol.l-1, SEM 4.5 basal, P less than 0.05). While concentrations of serum potassium, plasma adrenaline and cAMP returned to their basal levels immediately after exercise, those of plasma noradrenaline and serum aldosterone remained elevated 30 min later (1.90 nmol.l-1, SEM 0.01, P less than 0.01; and 0.85 nmol.l-1, SEM 0.12, P less than 0.01, respectively). Serum insulin concentration did not change during exercise (6.47 mlU.l-1, SEM 0.58 at the end of exercise vs 5.47 mlU.l-1, SEM 0.41 basal, NS) but increased significantly (P less than 0.02) at the end of the recovery period (7.12 mlU.l-1, SEM 0.65).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hormonal regulation of potassium shifts during graded exhausting exercise. 164 7

Amiloride-sensitive potassium secretion in response to acute potassium loading is lower in the newborn than in the adult. Potassium secretion is a function of late distal tubule and cortical collecting tubule Na,K-ATPase activity. Na,K-ATPase activity in vivo is determined by enzyme abundance and catalytic turnover. Chronic potassium supplementation increases potassium secretory capacity in the adult by increasing enzyme abundance in the late distal and cortical collecting tubules. We hypothesized that the lower potassium secretory capacity of the newborn was the result of lower late distal and cortical collecting tubule Na,K-ATPase activity and could be similarly enhanced. To test this hypothesis, newborn dogs were supplemented with 6 mmol KCl.d-1.kg-1 for 1 wk; age-matched litter mate controls were not (n = 8 pairs). Potassium supplementation resulted in a mean increase in Vmax Na,K-ATPase activity in vitro (proportional to pump abundance) of 70 +/- 42%. Mean Na,K-ATPase activities +/- SEM were 279 +/- 58 versus 198 +/- 44 nmol inorganic P. h-1.microgram DNA-1, p = 0.05. However, amiloride-sensitive potassium secretion after an acute potassium load of 20 mumol.min-1.kg-1 over 150 min was not enhanced (9.6 +/- 1.8 versus 8.9 +/- 0.8 mumol.min-1.kg-1, potassium-supplemented versus control animals). We conclude that lower enzyme abundance is not primarily responsible for the newborn's lower potassium secretory capacity. We speculate that the factor that limits secretion in the newborn during acute potassium loading does so by restricting catalytic turnover of the enzyme in vivo.
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PMID:The role of cortical Na,K-ATPase in distal nephron potassium secretion by the immature canine kidney. 166 96

The release of putative neurotransmitters [aspartate, glutamate, and gamma-aminobutyric acid (GABA)] was studied in hippocampal slices from adult normal C57BL/6J (B6) and El (epileptic) mice. The El mice, a genetic model of temporal lobe epilepsy, had an average of 86 seizures. Sets of B6 and El hippocampal slices (400 microns thick) were incubated in a series of normal and high potassium (60 mM) buffers in the presence or absence of calcium. The calcium-dependent and calcium-independent potassium-induced release of amino acids was compared in each mouse strain. Release of endogenous amino acids was measured using liquid chromatography with electrochemical detection and was expressed as picomoles of amino acid released per milliliter of incubation buffer per minute of incubation per slice +/- SEM. No significant differences were found between the El and B6 mice for the calcium-dependent potassium-evoked release of glutamate (18.20 +/- 2.62 and 15.41 +/- 3.56), or GABA (17.28 +/- 2.90 and 12.73 +/- 1.37), respectively. Aspartate release, however, was significantly higher in the El mice (6.62 +/- 0.69) than in the B6 mice (3.31 +/- 0.72). These findings suggest that enhanced aspartate release may be related to seizure expression in El mice.
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PMID:Enhanced aspartate release from hippocampal slices of epileptic (El) mice. 167 82

Nineteen patients undergoing elective gastrointestinal surgery were randomised to receive recombination human growth hormone (n = 9) or placebo (n = 10) for the first five postoperative days. All received epidural analgesia and total parenteral nutrition during the same period (energy supply 125% of basal metabolic rate, mean nitrogen (+/- SEM) 5.7 (+/- 0.1) g/m2). Nitrogen and potassium retention was induced in the growth hormone group compared with the placebo group (cumulative nitrogen balance 4.1 (+/- 1.1) g/m2 in the growth hormone group and -3.1 (+/- 1.8) g/m2 in the placebo group, p less than 0.01; cumulative potassium balance 80.8 (+/- 4.7) mmol/m2 in the growth hormone group and 43.1 (+/- 11.4) mmol/m2 in the placebo group, p less than 0.01). In the growth hormone group, serum glucose concentrations increased each evening and mean serum albumin concentrations were reduced throughout the period; the morning pulse rates were decreased, and the patients gained weight compared with the placebo group.
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PMID:Nitrogen retention caused by growth hormone in patients undergoing gastrointestinal surgery with epidural analgesia and parenteral nutrition. 167 77

In cystic fibrosis, cyclic adenosine monophosphate-mediated chloride secretion is abnormal in respiratory, small intestinal, and rectal mucosa. Calcium-mediated chloride secretion is also aberrant in CF small intestinal mucosa in cystic fibrosis, in contrast to the respiratory epithelia, where it appears to be normal. To determine whether this disparity between calcium- and cyclic adenosine monophosphate-mediated chloride secretion exists in cystic fibrosis rectal mucosa in vivo, transrectal potential difference was measured in age-matched adult cystic fibrosis subjects (n = 8) and control subjects (n = 9) in response to 10-minute luminal perfusions of bethanechol (1 mmol/L) or theophylline (5 mmol/L). In response to bethanechol, an initial (1-minute) negative change in potential difference (-1.4 +/- 1.1 mV; mean +/- SEM) was seen in control subjects, in contrast to a positive change in mean potential difference (+2.5 +/- 1.0 mV) in cystic fibrosis subjects (control vs. cystic fibrosis, P less than 0.05). After 1 minute, mean potential differences changes in both control and cystic fibrosis subjects were positive. Theophylline perfusion resulted in a significant (P less than 0.01) difference in potential difference response between groups; at 10 minutes, the potential difference became more negative (-3.6 +/- 1.4 mV) in control subjects and more positive in cystic fibrosis subjects (+3.9 +/- 1.4 mV). To determine whether second messenger-mediated potassium secretion contributed to the observed potential difference changes in response to bethanechol and theophylline, studies were repeated in the presence of barium chloride, a known blocker of potassium conductance. In the control group, barium chloride significantly enhanced the theophylline-induced negative potential difference change (P less than 0.05) and reduced the positive potential difference change seen with bethanechol alone. In subjects with cystic fibrosis, barium chloride completely abolished the previously seen positive potential difference change in response to either bethanechol or theophylline alone. These in vivo studies suggest that there is active potassium secretion in both control and cystic fibrosis rectal mucosa in response to cyclic adenosine monophosphate- and calcium-dependent secretagogues and that the magnitude of the potential difference changes attributable to barium-inhibitable potassium secretion is the same in cystic fibrosis and control subjects. In contrast, it appears that in cystic fibrosis rectal mucosa in vivo, calcium- as well as cyclic adenosine monophosphate-dependent chloride secretion is aberrant.
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PMID:In vivo evidence of altered chloride but not potassium secretion in cystic fibrosis rectal mucosa. 167 33

The use of recombinant human erythropoietin (rhuEPO) has revolutionized the treatment of renal anemia, but the dose regimens have not been established. We studied the effects of subcutaneous rhuEPO given 4,000U (1 vial) every 5-10 days in 9 patients on continuous ambulatory peritoneal dialysis (CAPD). Ten stable CAPD patients (6 females and 4 males; mean age +/- SEM, 54.4 +/- 5.6 years; mean baseline hemoglobin concentration 7.3 +/- 1.2g/dL) were commenced on s.c. rhuEPO. None of the patients had a history of gastrointestinal bleeding, aluminum overload, sepsis nor receiving androgens. Seven patients were receiving 4,000 U rhuEPO weekly, one patient each was receiving 4,000 U every 5 and 10 days (range, 66.7-89.3 U/kg/week). The dose was adjusted every 4 weeks according to response by altering the dose interval. The mean hemoglobin concentration increased from 7.3 +/- 1.2 g/dL to 10.3 +/- 1.1 g/dL over 8 weeks. There was no significant changes in the serum ferritin, urea, creatinine and potassium levels. One patient required an increase in antihypertensive therapy. We feel that s.c. rhuEPO 4,000 U given on an intermittent basis is effective in the treatment of anemia in CAPD patients. The administration of a single vial each time is convenient and cost sparing. The gradual rise in hematocrit avoids complications.
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PMID:Subcutaneous recombinant human erythropoietin in patients on CAPD. 168 Apr 47


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