Gene/Protein Disease Symptom Drug Enzyme Compound
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Seven severely obese, outpatient dieters lost weight (mean +/- SEM, 14 +/- 1 kg), and the composition of weight lost was determined by six different models. Total body water (TBW), total body potassium (TBK), and body density, bone mineral content, and fat as determined by dual photon absorptiometry (DPA) were measured while subjects were weight-stable, before and after weight loss. Fat loss was calculated by three two-compartment models (2C-TBW, 2C-TBK, and hydrodensitometry [2C-HD]), one three-compartment model (HD with correction for water content of fat-free mass [FFM], 3C), and one four-compartment model (HD with correction for water and mineral content of FFM, 4C), and was measured directly by DPA. Mean composition of weight loss was similar for all models (mean weight lost as fat: 89% for DPA, 91.5% for 4C, 89% for 3C, 88.6% for 2C-HD, and 87% for 2C-TBW) except 2C-TBK (weight lost as fat, 66%). There was a much wider range of individual values for the 2C-TBW and 2C-TBK models (17% to 138% and 18% to 93%, respectively) than for the multicompartment models (63% to 112%) and DPA (76% to 107%). Almost opposite results were obtained for the same individual when using the 2C-TBK and 2C-TBW models. The discrepancy between these models was due to the inverse relationship between changes in TBW and TBK in the group as a whole (r = -.34, NS). In addition, TBK loss was found to be dependent on the initial level of hyperinsulinemia, calculated as the area under the 2-hour oral glucose tolerance curve.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Composition of weight loss in severely obese women: a new look at old methods. 140 93

The renal effects of pulsatile (pulse pressure 18.0 +/- 1.5 mm Hg [mean +/- SEM]) or nonpulsatile perfusion (mean pulse pressure 1.9 +/- 0.4 mm Hg) during either alpha-stat (mean PaCO2 41.2 +/- 0.9 mm Hg measured at 37 degrees C) or pH-stat (mean PaCO2 60.6 +/- 1.7 mm Hg measured at 37 degrees C) pH management of hypothermic cardiopulmonary bypass (CPB) were studied in 100 patients undergoing elective coronary artery bypass surgery. Mean urine output, fractional excretion of sodium and potassium, and renal failure index all increased during the study period; however, there was no difference among the four different CPB management groups. Mean postoperative creatinine and blood urea nitrogen values decreased compared with preoperative values, again without differences among treatment groups. Three patients developed acute renal insufficiency; of these, two had received nonpulsatile perfusion and pH-stat management, and the other had been managed with pulsatile perfusion and pH-stat management. These three patients all had undergone prolonged CPB and required at least two vasoactive drugs and the use of an intraaortic balloon pump to be weaned from CPB. In patients with normal preoperative renal function undergoing hypothermic CPB, neither the mode of perfusion, pulsatile or nonpulsatile, nor the method of pH management, pH-stat or alpha-stat, influences perioperative renal function.
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PMID:Differences in pH management and pulsatile/nonpulsatile perfusion during cardiopulmonary bypass do not influence renal function. 141 20

Cromakalim (BRL 34915) is a potassium channel opener with therapeutic potential as a bronchodilator in asthma. Cromakalim (0.1-30 mumol/l) inhibited the spontaneous tone of human isolated bronchi in a concentration-related manner being nearly as effective as isoprenaline or theophylline. The order of relaxant potencies (expressed as -log10 IC50 mol/l; mean +/- SEM) was isoprenaline (7.29 +/- 0.27; n = 8) > cromakalim (5.89 +/- 0.12; n = 7) > theophylline (4.07 +/- 0.13; n = 10). In human bronchi where tone had been raised by addition of histamine (0.1 mmol/l), acetylcholine (0.1 mmol/l) or leukotriene D4 (LTD4, 0.1 mumol/l), the relaxant effect of cromakalim was substantially reduced. Cromakalim suppressed the contraction produced by KCl (25 mmol/l) but not that produced by KCl (120 mmol/l). Tetraethylammonium (8 mmol/l) was without effect against the relaxant action of cromakalim but procaine (0.5-5 mmol/l) and glibenclamide (0.3 mumol/l) antagonised it. Cromakalim (10 mumol/l) produced an upward displacement of concentration-effect curves for KCl (1-100 mmol/l), acetylcholine (1 nmol/l-1 mmol/l) and histamine (1 nmol/l-1 mmol/l) but it did not alter the concentration-effect curve for LTD4 (0.1 nmol/l-0.1 mumol/l). When tissues were challenged in the presence of cromakalim (10 mumol/l) with KCl (100 mmol/l), acetylcholine (1 mmol/l) or histamine (1 mmol/l), an enhanced contraction was observed compared to control tissues. This enhancement by cromakalim was absent when tissues were challenged with acetylcholine or histamine in either a Ca(2+)-free medium (plus EGTA 0.1 mmol/l) or in the presence of verapamil (10 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The relaxant effects of cromakalim (BRL 34915) on human isolated airway smooth muscle. 143 31

Maximum preservation times of 4-6 hr continue to plague lung transplantation. The high-potassium colloid University of Wisconsin solution (UWS) has proved superior to the crystalloid modified Eurocollins' solution (ECS) for preservation of the liver, kidney, and pancreas. The purpose of this study was to compare UWS and ECS for extended lung preservation using a technique of combined pulmonary and bronchial artery perfusion. Simultaneous pulmonary artery and bronchial artery (via a closed aortic segment) perfusion was employed to harvest the lungs of ten mongrel dogs (wt 25-35 kg) using either UWS (n = 5) or ECS (n = 5) preservation solutions. Following 17 hr of cold (4 degrees C) pulmoplegic storage, the lungs were placed in an isolated perfused working lung (IPWL) apparatus. Seven freshly harvested lungs served as a control group (CON). Lung aerodynamics and gas exchange were evaluated at standard intervals until failure of the lung on the IPWL apparatus. Time until failure (mean +/- SEM) for each group was: CON = 209 +/- 14 min; UWS = 227 +/- 26 min; and ECS = 123 +/- 29 min. Only one of the ECS lungs lasted longer than 90 min. UWS-preserved lungs displayed a gas exchange efficiency equal to the CON group and better than that in the ECS-preserved lungs (lower A-aDO2, lower intrapulmonary shunt), suggesting better protection of the alveolar capillary membrane. Although the UWS lungs were initially less compliant than the ECS lungs, at no time was there a significant difference in the total work of respiration between the two groups. We conclude that UWS provides superior protection of the alveolar capillary membrane. The aerodynamic disadvantages of UWS preservation did not effect lung survival or total work of respiration.
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PMID:Successful extended lung preservation with UW solution. 144 Aug 42

We studied uptake of L-triiodothyronine (T3) by the human choriocarcinoma cell line, JAR. Uptake was time dependent with a half-time of 56.2 +/- 7.2 min (mean +/- SEM, n = 4). A non-saturable component accounted for about 24% of total uptake. We found a single saturable uptake mechanism with a calculated Michaelis constant (Km) of 586 +/- 206 nM (n = 9) and a corresponding maximum velocity of 17.0 +/- 5.7 pmol/min per mg protein (n = 9), values similar to those we have described recently in cultured normal human trophoblast cells. Uptake was dependent on temperature and intracellular energy, being reduced at lower temperatures and in the presence of potassium cyanide. It was independent of the Na+ gradient across the cell membrane and the presence of Na+ in the external medium, but was affected by the cell membrane potential.
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PMID:Membrane transport of thyroid hormone in the human choriocarcinoma cell line, JAR. 144 86

Cerebrospinal fluid and serum were obtained from 16 clinically normal adult cows (11 dairy, 5 beef). Sodium, potassium, magnesium, total protein, and albumin concentrations, osmolality, and lactate dehydrogenase and creatine kinase activities, were quantified in CSF and serum. Total and differential cell counting, protein electrophoresis, and IgG quantification were performed on CSF. Statistical analyses of these variables, including mean, SEM, range, and 95% confidence intervals, were performed. Effects of blood contamination were evaluated, and were found to be negligible for all measured constituents. Correction factors for CSF creatine kinase and lactate dehydrogenase activities accounting for cellular contamination were developed. Total nucleated cell count was similar to counts in CSF of other species, but higher than values in healthy people. Differential leukocyte count in CSF was similar to that reported in CSF of other domestic animals: mostly lymphocytes, fewer monocytoid cells, and scant neutrophils. Cerebrospinal fluid protein concentration was higher than concentration reported for dogs, goats, and people, but was similar to values reported for horses. Beef cows had higher CSF total protein concentration than did dairy cows; also, beef cows had higher CSF gamma-globulin concentration. The concentration of sodium in CSF was slightly higher than the value in serum, and potassium concentration was lower than the value in serum. In contrast to studies of human beings, CSF osmolality was generally less than serum osmolality in the cows studied. Reference values for CSF electrolyte concentrations and osmolality are useful for diagnosis of salt poisoning and for assessment of the effects of fluid therapy. Magnesium concentration was lower in CSF, compared with serum.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Composition and analysis of cerebrospinal fluid in clinically normal adult cattle. 146 1

Variation of PCO2 with concomitant changes in extracellular pH (pHo) may modulate cerebrovascular resistance, but the direct actions of carbon dioxide and pHo on human cerebral arteries are unknown. In this study, we have evaluated the effects of different carbon dioxide tensions (2.7, 4.2 and 7.2 kPa) with either fixed (pHo = 7.44) or concomitant changes in pHo, on contractions induced by depolarization (potassium) or receptor stimulation (prostaglandin F2 alpha) in isolated human pial arteries. Isolated changes in PCO2 had no significant effect on either potency (unchanged EC50 value) or the maximum response (Emax) in potassium-contracted arteries. Hypercapnia with uncompensated pHo significantly decreased both EC50 and Emax values, whereas uncompensated hypocapnia significantly increased the EC50 value without any effect on Emax. Concentration-response curves induced by prostaglandin (PG) F2 alpha were shifted significantly to the right (increased EC50 = decreased potency) during both hypo- and hypercapnia, independent of changes in pHo. The maximal responses were enhanced significantly during hypocapnia (Emax = 110 (SEM 2)%), but this enhancement was converted into a slight attenuation when pHo was compensated (Emax = 92 (4)%). Hypercapnia, with or without compensation of pHo, decreased the Emax values to 69 (16)% and 73 (9)%, respectively. We conclude that hypocapnia increases contractility in human pial arteries--an effect which is reversed by compensation of pHo. In contrast, the hypercapnic decrease of PGF2 alpha-induced contractions appears to be independent of pHo. The results confirm a relationship between contractility and pHo, but do not exclude a direct action of carbon dioxide in receptor-stimulated arteries.
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PMID:Modulation by carbon dioxide and pH of the contractile responses to potassium and prostaglandin F2 alpha in isolated human pial arteries. 146 6

Thirty women in their third trimester of pregnancy (37-42 weeks), 40 women during and 72 h after labour and 18 non-pregnant controls were studied for changes in serum and mononuclear cell cation content, and their relationship to cervical effacement and intensity of pain as measured by plasma beta endorphin concentrations during labour. Serum magnesium fell from 0.95 +/- 0.01 (mean +/- SEM) to 0.84 +/- 0.02 mmol/litre at late pregnancy and further to 0.76 +/- 0.01 during labour (P < 0.001); serum potassium fell from 4.25 +/- 0.05 to 3.79 +/- 0.06 mmol/litre (P < 0.0001) during labour; and serum calcium fell from 2.40 +/- 0.02 to 2.28 +/- 0.01 mmol/litre at late pregnancy (P < 0.001) and further to 2.25 +/- 0.02 mmol/litre during labour (P < 0.001). Mononuclear cell magnesium content rose from 4.5 +/- 0.3 to 5.6 +/- 0.04 fmol/cell (P < 0.02); potassium content rose from 37.7 +/- 2.0 to 50.9 +/- 3.0 fmol/cell (P < 0.001); and calcium content rose from 4.4 +/- 0.4 to 7.6 +/- 1.1 fmol/cell (P < 0.105). On the other hand, mononuclear cell sodium content fell from 7.2 +/- 0.5 to 3.8 +/- 0.3 fmol/cell (P < 0.001). Plasma beta endorphin concentrations increased with increasing degrees of effacement, as did intracellular Na, whereas intracellular Mg and K showed an inverse trend. A significant correlation was found between intracellular cation and beta endorphin levels (r = -0.98, Mg; -0.99, K; 0.83, Na). These changes are probably due either to intercompartmental cation shifts or possibly to endometrial ischaemia and damage during labour.
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PMID:Serum and mononuclear cell potassium, magnesium, sodium and calcium in pregnancy and labour and their relation to uterine muscle contraction. 146 54

We investigated the basis for the alterations in the intracellular potassium and sodium activity occurring in subendocardial Purkinje fibers surviving in 24-hour infarcts by examining ion activities in these Purkinje fibers removed from infarcting hearts at earlier times. Specifically, we examined intracellular potassium activity, sodium activity, and pH at 1 and 3 hours after ligation of the left anterior descending coronary artery, and we correlated the changes in ion activity with changes in maximum diastolic potential. We tested various mechanistic hypotheses relating to how the ion activity changes develop and how they affect membrane potential. We found that intracellular sodium activity in tissue removed 1 hour after ligation was on average already maximally elevated by a factor of 2 over control (19.2 +/- 2.0 mM [mean +/- SEM] versus 9.4 +/- 0.4 mM). Potassium activity diminished progressively over the first 24 hours (from normal of 112.0 +/- 2.7 to 61.6 +/- 2.8 mM), although half of the decrease occurred during the first hour (to 86.8 +/- 4.1 mM). Intracellular pH did not change at either 1 or 3 hours. Whereas maximum diastolic potential depolarization exceeded the calculated depolarization of the potassium equilibrium potential by a factor of 2 in 24-hour infarcts, the depolarization at 1 and 3 hours could be more nearly attributed to the loss of potassium. The change in the dependence of maximum diastolic potential on potassium equilibrium potential may be due to changes in membrane conductance caused by ionic or biochemical factors. The changes in ion activity continuously develop during the first day after ligation and may be due to multiple factors and mechanisms.
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PMID:Time course of changes in intracellular K+, Na+, and pH of subendocardial Purkinje cells during the first 24 hours after coronary occlusion. 153 92

Twenty-four dogs with induced, severe chronic renal failure were allotted to 2 groups of 12 each. Group-A dogs were fed a 0.4% phosphorus (P)/0.6% calcium, 32% protein diet, and group-B dogs were fed a 1.4% P/1.9% calcium, 32% protein diet. Dogs were studied over 24 months to determine clinical status, survival, blood biochemical alterations, glomerular filtration rate (GFR), urinary excretion of P and protein, renal morphologic changes, and renal tissue concentrations of calcium, P, and magnesium. Group-A dogs developed statistically significant differences from group-B dogs in several blood biochemical values (PCV and total solids, calcium, P, potassium, sodium, chloride, total CO2 (TCO2), anion gap, and parathyroid hormone concentrations) and in urinary P excretion. Mean (+/- SEM) GFR values in group-A and group-B dogs were nearly identical when diets were initiated (group A = 0.73 +/- 0.05 ml/min/kg of body weight; group B = 0.72 +/- 0.08 ml/min/kg), but significantly (P = 0.0346) lower GFR developed in group-B than in group-A dogs over time. At 24 months, GFR in survivors was 0.83 +/- 0.08 and 0.63 +/- 0.15 ml/min/kg for dogs of groups A and B, respectively. Other measurements favored the hypothesis that P/calcium restriction was beneficial, but values failed to reach statistical significance. Survival was greater at 24 months in group-A than in group-B (7 vs 5) dogs, and renal tissue concentrations of calcium and P were higher in group-B than in group-A dogs. Differences were not detected between groups in urinary excretion of protein and in the type or severity of renal lesions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of phosphorus/calcium-restricted and phosphorus/calcium-replete 32% protein diets in dogs with chronic renal failure. 153 11


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