Double-indicator Method Research Articles

Antibacterial susceptibility and Invitro effect of sodium chloride, magnesium ions, and serum on Staphylococcal-β-lactamase production in Ekpoma Nigeria.

Background: Resistance to agents of tropical infections remains a public health challenge especially in resource-poor countries despite the efforts by multiple disciplines to face the challenges. Objectives: This study was carried out to determine the effects of sodium chloride, magnesium ion, and serum on beta-lactamase production; and the antibiotic susceptibility pattern of staphylococci strains isolated from clinical samples from Irrua Specialist Teaching Hospital, Edo State, Nigeria. Methods: Thirty-five (35) clinical isolates were collected and screened for the presence of beta-lactamase production using standard microbiological procedures, the staphylococci isolates were subjected to antibiotic susceptibility tests using the disc diffusion method, and beta-lactamase production test was carried out using starch paper hydrolysis. The effects of various concentrations of sodium chloride (0.1 – 7.0%), magnesium tetra oxo sulphate (VI) (0.1 – 1.0%), and serum (1 – 20%) on beta-lactamase production by the staphylococci were assayed using the double indicator method. Results: Of the 35 staphylococci, isolates identified, 23 were S. aureus, and the remaining 12 were coagulase-negative staphylococci. Out of all the 35 isolates, 7 isolates (20%) were beta-lactamase producers, with 4 being S. aureus and 3 being coagulase-negative staphylococci. The staphylococci isolates showed a high level of resistance (71.4 – 97.1%) to the antibiotics used. Conclusion: Beta-lactamase production was enhanced by NaCl and serum at a high concentration, but when subjected to statistical analysis individually it was not significant p>0.05, when compared against each other it was significant p<0.05. Mg2+ was inhibitory at higher concentration of 1.0%, 5.0% and 7.0% with p >0.05. This study indicates that Mg2+ could be used as a beta-lactamase inhibitor in the manufacturing of beta-lactam antibiotics.

Seasonal variability of palatability and nutrient intake in different age groups of range sheep

ABSTRACT The study was designed to analyze the seasonal dynamics of the nutritive value of endemic plant species (Berberis lycium, Indigofera heterentha, Parrotiopsis jacquemontiana, Rosa macrophylla and Rosa webbiana) and composite pasture grasses in different age groups of sheep using double indicator method. Twenty Kashmir Merino sheep from the two age groups in each season of summer (June) and autumn (October) were selected and divided into Group I (about 4 months of age) and Group II (1–2 years of age) in a 2 × 2 factorial design. The metabolizable energy (ME) of plants and composite grasses range from 10.11 to 12.60 and 7.32 to 9.94 MJ/kg, respectively, across different seasons. The quality of plants and the composite grass samples, measured in terms of total digestible nutrients, ME, crude protein and fiber content deteriorated with the advancement of the season. Palatability, nutrient and mineral intake, D and relative feed quality values were better during the summer than the autumn season. ME intake in younger sheep (Group I) was deficient by 32.5% compared to maintenance requirements during the autumn season. It was found that adult sheep tend to optimize their energy requirements from pastures while younger sheep fail to do so. Abbreviations: ADF: Acid Detergent Fiber; ADL: Acid Detergent Lignin; Ca: Calcium; CP: Crude Protein; D value: Digestible organic matter in dry matter; DCP: Digestible Crude Protein; DMI: Dry Matter Intake; EE: Ether Extract; ME: Metabolizable Energy; NDF: Neutral Detergent Fiber; OM: Organic Matter; P: Phosphorus; RFI: Relative Feed Index; TDN: Total Digestible Nutrients

Effective identification of (NH4)2CO3 and NH4HCO3 concentrations in NaHCO3 regeneration process from desulfurized waste

This work describes the quantitative analysis of (NH4)2CO3 and NH4HCO3 using a simple solution phase titration method. Back titration results at various (NH4)2CO3-NH4HCO3 ratios demonstrated that 6:4 ratio caused a 3% error in their differentiation, but very high errors were found at other ratios. A similar trend was observed for the double indicator method, especially when strong acid HCl was used as a titrant, where still less errors (2.5%) at a middle ratio of (NH4)2CO3-NH4HCO3 was found. Remaining ratios with low (NH4)2CO3 (2:8, 4:6) show high +ve error (found concentration is less) and high (NH4)2CO3 (7:3, 8:2, and 9:1) show high -ve error (found concentration is higher) and vice versa for NH4HCO3. In replacement titration using Na2SO4, at both higher end ratios of (NH4)2CO3-NH4HCO3 (2:8 and 9:1), both -ve and +ve errors were minimized to 75% by partial equilibrium arrest between (NH4)2CO3 and NH2COONH4, instead of more than 100% observed in back titration and only double indicator methods. In the presence of (NH4)2SO4 both -ve and +ve error% are completely reduced to 3±1 at ratios 2:8, 4:6, and 6:4 of (NH4)2CO3-NH4HCO3, which demonstrates that the equilibrium transformation between NH2COONH4 and (NH4)2CO3 is completely controlled. The titration conducted at lower temperature (5 °C) in the presence of (NH4)2SO4 at higher ratios of (NH4)2CO3-NH4HCO3 (7:3, 8:2,and 9:1) shows complete minimization of both -ve and +ve errors to 2±1%, which explains the complete arresting of equilibrium transformation. Finally, the developed method shows 2±1% error in differentiation of CO3(2-) and HCO3(-) in the regeneration process of NaHCO3 from crude desulfurized sample. The developed method is more promising to differentiate CO3(2-) and HCO3(-) in industrial applications.

Evaluation of the effectiveness of the double indicator method of scintigraphy in the differential diagnosis of thyroid nodules

Aim. To evaluate the effectiveness of double indicator scintigraphy in the differential diagnosis of thyroid nodules. Methods. Analyzed was the data of radionuclide investigations of 25 patients with thyroid disease at the age of 36 to 72 years, who were operated on in 2009-2011. The radioisotope study was conducted in two stages. Evaluation of the scintigraphic uptake pattern of the radiopharmaceutical in the studied areas was performed visually and quantitatively. Results. The scintigraphic results were compared with cytological and histological studies. In the diagnosis of papillary thyroid cancer the sensitivity of the radioisotope investigation was 95%, specificity - 92%, diagnostic accuracy - 94%. The method was less precise and specific in the diagnosis of follicular cancer and macro-micro follicular adenomas (it gave positive results in the cases of adenoma and negative results in cases of follicular thyroid cancer). On average, the specificity of the double-phase radioisotope scintigraphy method using 99mTc-pertechnetate and technetril (99mTc-MIBI) in our study was 69%, accuracy - 75%, sensitivity - 79%. Conclusion. Radionuclide double-phase scintigraphy with the usage of 99mTc-pertechnetate and technetril (99mTc-MIBI) - is a highly informative method for the differential diagnosis of thyroid nodules, which can be used during atypical sonographic patterns and in the absence of clear histological data.

Energy partition for maintenance and weight gain in Nellore and crossbred steers finished under grazing

The objective of this work was to estimate net energy (NEm) and metabolizable energy (MEm) requirements for maintenance and efficiency of use of metabolizable energy for maintanence (k m) and gain (k g) of grazing Nellore and crossbred steers. It was used 24 castrated steers, 12 Nellore breed (386 kg SBW) and 12 ½ Limousin-Nelore crossbred (397 kg SBW). The comparative slaughter method was used. In each genetic group, animals were grouped in three similar groups: reference; restrict feeding and ad libitum feeding. The reference group was slaughtered in the beginning of the experiment whereas the others were slaughtered at the end of it. During the 104 days of the experimental period, the group under restrict feeding had access to pastures for 3.5 hours daily whereas the group with ad libitum feeding remained on pasture full time. Forage intake was estimated in two trials by using the double-indicator method. Values of NEm, MEm, k m and k g were estimated on the basis of empty body weight (EBW) through linear and non-linear model fitting. Requirements of NEm and MEm did not differ among Nellore and crossbred animals. In the linear model, the following results were obtained: Requirements of NEm = 86 kcal/kg0.75; requirements of MEm = 136 kcal/kg0.75 and k m = 0.63. Kg value was higher for Nellore animals (0.39) than for crossbred animals (k g = 0.33). Requirement of net energy of maintenance does not differ among grazing Nellores and ½ European-Nellore crossbred. For the same body weight, Nellore animals present greater fat proportion in gain composition than ½European-Nelore crossbred.

Measurement of extravascular lung water in patients with pulmonary edema

measurement of extravascular lung water has been a topic of major interest for more than two decades ([1][1], [5][2], [19][3]). In the recent article by Effros et al. ([2][4]), they provide a review of current and past efforts to measure extravascular lung water with thermal and osmotic dilution

What happens after pneumonectomy? A prospective study using the transpulmonary thermodilution method

event is the augmentation of the extravascular lung water (EVLW) that transudates into the alveolar space, impairing ventilation. In the experimental model, thoracotomy, rapid fluid infusion, and manipulation of the lung result in an increase in EVLW. 3 In humans, the transpulmonary thermodilution method is a reliable technique for EVLW assessment, even if a moderate overestimation as compared with the double-indicator method is expected in case of pneumonectomy. 4 Given the paucity of available information, this studywas designed tomonitor EVLW modifications occurring early after pneumonectomy in humans.

Seasonal variation of nutrient intake and digestibility of forage in beef cows grazed on a dwarf bamboo (Pleioblastus argenteostriatus f. glaber) dominant pasture

AbstractDwarf bamboo is a significant but unique native forage for cattle grazing in Japan. A pasture dominated by Pleioblastus argenteostriatus f. glaber, a type of dwarf bamboo, was used to evaluate nutrient intake, digestibility of forage and nutritional status of grazing cows. Eight Japanese Black cows were grazed on the pasture, and six among the eight grazing cows were used for the experiment. This experiment consisted of three periods: spring (May), summer (July) and autumn (September–October) in 2002 and 2003. The nutrient intake and digestibility of the cows were estimated by the double indicator method with chromic oxide (Cr2O3) as the external indicator and acid detergent insoluble ash (ADIA) in forages as the internal indicator. The crude protein (CP) and neutral detergent fiber (NDF) contents of forage selected by the cows hardly changed during the grazing seasons in both years. Crude ash, acid detergent lignin (ADL), ADIA, and acid detergent insoluble protein (ADIP) contents were the highest in autumn in both years. Nutrient intake of the cows was lower in autumn than in other seasons. Nutrient digestibility of the cows increased slightly from spring to summer and then decreased in autumn. Metabolizable energy (ME) intake satisfied the maintenance requirements of the cows in spring and summer; however, it was only 50%–70% of the maintenance in autumn for both years. Urea nitrogen concentration in plasma was always high, approximately 20 mg dL−1, during grazing periods. Inorganic phosphate (IP) concentration in plasma was lower than critical value (4.5 mg dL−1) in spring and autumn. Therefore, energy and phosphate supplementation are needed for the cows grazed on P. argenteostriatus f. glaber‐dominated pasture.

Wykorzystanie chlorofilu do oceny pobrania i strawności składników pokarmowych na pastwisku

Two experiments involving 8 adult ewes were carried out. In experiment No. 1 the sheep were fed exclusively on the pasture, whereas in the second experiment the green forage was supplied to sheep individually in feeding racks, to compare the roughage intake values to the results obtained using markers-based evaluation. In the studies, the double indicator method was applied, using the following markers: internal – chlorophyll and external – chromium oxide (Cr2O3). To evaluate potential changes of chlorophyll concentration in the samples, it was established three times: directly after sample collection, in the sample chilled to 0–4 centigrade and in the frozen sample. The average amount of dry matter consumed by all the sheep, established by weighing did not differ significantly from the amount assessed on the basis of chlorophyll A. The differences between the dry matter consumption related to 1 kg of BW0,75 in the experiments No. 1 and No. 2 resulted from the experimental animals weight gain during the studies. The sensitivity of chlorophyll A as a marker helpful for nutrients digestibility trials was also satisfactory. It stems from directional changes of digestibility coefficients, related to changes in the chemical composition of examined pasture roughage.

Factors influencing the estimation of extravascular lung water by transpulmonary thermodilution in critically ill patients*

To investigate factors that may influence the estimation of extravascular lung water (EVLW) with a single (cold) indicator compared with assessment using two indicators (thermo-dye dilution). Post hoc analysis of an electronic hemodynamic database. Surgical intensive care unit of a university hospital. Forty-eight critically ill patients monitored by the thermo-dye dilution technique in the postoperative period. None. The EVLW was simultaneously assessed by the thermo-dye dilution technique (EVLWref) and estimated by transpulmonary thermodilution (EVLWest). EVLWref index ranged between 1 and 40 mL/kg (mean 10 +/- 7 mL/kg) and EVLWest between 2 and 39 mL/kg (mean 9 +/- 6 mL/kg). EVLWref was closely correlated (r = .96) with EVLWest. The mean difference (bias) between EVLWref and EVLWest was -0.5 +/- 1.9 mL/kg. The bias was not influenced by the weight, height, body surface area, body mass index, Pao2, intrathoracic blood volume, cardiac output, or dosage of vasoactive agents. In contrast, the bias was slightly but significantly influenced by EVLWref, Pao2/Fio2 ratio, tidal volume, and level of positive end-expiratory pressure. In our surgical intensive care unit population, the estimation of EVLW by transpulmonary thermodilution was influenced by the amount of EVLW, the Pao2/Fio2 ratio, the tidal volume, and the level of positive end-expiratory pressure. However, compared with the double indicator method, transpulmonary thermodilution estimation remained clinically acceptable even in patients with severe lung disease.

Effect of the Geographic Breeding Region on Digestible Energy Intake and Growth Rate of Thoroughbred Yearling Horses: A Comparison of the Hidaka and Miyazaki Regions of Japan

Different geographic regions in which thoroughbred yearling horses are bred have different climates and different types of forage in pasture and hay. These factors are likely to influence the energy metabolism and growth rate of yearling horses. However, the effects of the characteristics of geographic regions on the digestible energy (DE) intake and growth rate of thoroughbred yearlings has yet to be clarified in detail. Here, we have examined the effect of the breeding region on growth performance of young horses, by comparing the DE intakes and growth rates of thoroughbred yearlings in Hidaka (Hokkaido) and Miyazaki (Southern Kyushu) in Japan. Eighteen male thoroughbred yearlings were divided equally into two groups, and bred either at the Hidaka training and research center (HYF) or the Miyazaki yearling farm (MYF). Measurements were conducted in September (summer) and in February (winter), and the mean ages of the yearlings during these two periods were 18 months and 23-24 months old, respectively. The apparent digestible energy intake was measured by a double-indicator method using Cr2O3 and lignin. There was no significant difference in the DE intakes between the yearling horses at the HYF and MYF in either season. The warm land of Southwest Japan has been considered to be unsuitable for growing forage containing sufficient nutrients to feed thoroughbreds, but no nutritional disadvantage of this forage was detected in the yearlings bred at the MYF. On the other hand, the heart girth (HG) and cannon circumference (CC) were found to be significantly smaller in yearlings at the HYF, compared to those at the MYF, in the winter evaluation (p<0.05). Significant positive correlations between the ADG and DE intake/100 kg body weight were seen in animals at the HYF in the summer and in those at the MYF in both seasons; however, such a correlation was not found in horses at the HYF in winter. The reason for the smaller HG and CC and the absence of a significant correlation between the ADG and DE intake/100 kg body weight in the yearlings at the HYF in winter is unclear. It could be attributable to growth delay due to exposure to cold temperatures, or lack of supplementation to compensate for the increased energy requirement due to excess energy metabolism in cold weather. Closer attention must, therefore, be paid to the energy supply and nutritional composition of feedstuffs fed to thoroughbred yearlings at farms in regions with cold ambient temperatures.

Lung perfusion affects preload assessment and lung water calculation with the transpulmonary double indicator method.

The transpulmonary double indicator method uses intra- and extravascular indicators to calculate cardiac output, intrathoracic blood volume, global end-diastolic volume, and extravascular lung water content. Since lung perfusion may be of importance during these measurements, we studied the effects of pulmonary blood flow occlusion on measurements obtained with this method. Experimental animal facility of a University department. In seven pigs, the branch of the pulmonary artery perfusing the lower and middle lobe of the right lung was occluded. Measurements before, during, and after the occlusion were made with a pulmonary artery catheter and a commonly used transpulmonary double indicator catheter and device. Occlusion of the right lower and middle lobe branch of the pulmonary artery increased mean pulmonary pressure (before occlusion: 24+/-1, during occlusion: 32+/-2, after reopening 25+/-1 mmHg; P<0.05), increased right ventricular end-diastolic volume (172+/-34, 209+/-21, 174+/-32 ml, respectively; P<0.05), decreased intrathoracic blood volume (998+/-39, 894+/-48, 1006+/-49 ml, respectively; P<0.05), and decreased extravascular lung water (7.2+/-0.5, 4.2+/-0.4, 6.9+/-0.4 ml/kg, respectively; P<0.05) without causing significant changes in cardiac output. All changes were reversible upon reopening the vessel. These data show that the transpulmonary double indicator method may underestimate extravascular lung water and right ventricular preload when the perfusion to parts of the lung is obstructed.

Blood-brain barrier transport and brain metabolism of glucose during acute hyperglycemia in humans.

It is controversial whether transport adaptation takes place in chronic or acute hyperglycemia. Blood-brain barrier glucose permeability and regional brain glucose metabolism (CMR(glc)) was studied in acute hyperglycemia in six normal human subjects (mean age, 23 yr) using the double indicator method and positron emission tomography and [(18)F]fluorodeoxyglucose as tracer. The Kety-Schmidt technique was used for measurement of cerebral blood flow (CBF). After 2 h of hyperglycemia (15.7 +/- 0.7 mmol/L), the glucose permeability-surface area product from blood to brain remained unchanged (0.050 +/- 0.008 vs. 0.059 +/- 0.031 mL/100 g.min). The unidirectional clearance of [(18)F]fluorodeoxyglucose (K(1)*) was reduced from 0.108 +/- 0.011 to 0.061 +/- 0.005 mL/100 g.min (P < 0.0004). During hyperglycemia, global CMR(glc) remained constant (21.4 +/- 1.2 vs. 23.1 +/- 2.2 micromol/100 g.min, normo- and hyperglycemia, respectively). Except for a significant increase in white matter CMR(glc), no regional difference in CMR(glc) was found. Likewise, CBF remained unchanged. The reduction in K(1)* was compatible with Michaelis-Menten kinetics for facilitated transport. Our findings indicate no major adaptational changes in the maximal transport velocity or affinity to the blood-brain barrier glucose transporter. Finally, hyperglycemia did not change global CBF or CMR(glc).

Lung vessel occlusion and validity of transpulmonary double-indicator method

Lung vessel occlusion and validity of transpulmonary double-indicator method

No effect of insulin on glucose blood-brain barrier transport and cerebral metabolism in humans.

The effect of hyperinsulinemia on glucose blood-brain barrier (BBB) transport and cerebral metabolism (CMRglc) was studied using the intravenous double-indicator method and positron emission tomography using [18F]fluorodeoxyglucose as tracer (PET-FDG). Sixteen normal healthy control subjects (25 +/- 4 years old) were studied twice during a euglycemic and a euglycemic-hyperinsulinemic condition. Our hypothesis was that high physiologic levels of insulin did not affect the BBB transport or net metabolism of glucose. During insulin infusion, arterial plasma insulin levels increased from 48.5 to 499.4 pmol/l. The permeability-surface area products for glucose and FDG BBB transport obtained with the double-indicator method remained constant during hyperinsulinemia. Similarly using PET-FDG, no changes were observed in the unidirectional clearance of FDG from blood to brain. k2* (FDG transport from brain to blood) increased significantly by 15 and 18% (gray and white matter, respectively), and k4* (dephosphorylation of FDG) increased by 18%. The increase in k2* may be caused by insulin inducing a decrease in the available FDG brain pool. The increase in k4* may be related to an increased loss of labeled products during insulin fusion. Irrespective of these changes, CMRglc remained unchanged in all brain regions. We conclude that hyperinsulinemia within the normal physiologic range does not affect BBB glucose transport or net cerebral glucose metabolism.

High dose insulin does not increase glucose transfer across the blood-brain barrier in humans: a re-evaluation.

This study re-evaluates previously published data on blood-brain barrier transfer coefficients in humans exposed to high insulin levels. In this study of seven volunteers, global blood-brain barrier permeability to glucose and phenylalanine was measured by means of the intracarotid double-indicator method before, during, and after an insulin-glucose clamp. Data were reanalyzed by means of a mathematical model that takes capillary heterogeneity and labelled glucose backflux from the brain into account. The permeability-surface area product (PS) for glucose transport from the blood into the brain, PS1, was 0.145 (0.102-0.211) (median and quartiles), 0.146 (0.113-0.259), and 0.157 (0.133-0.181) ml g-1 min-1 before, during, and after insulin challenge, respectively. In six of the subjects, PS for transport from brain to blood over the brain glucose distribution volume, PS2/Ve decreased under hyperinsulinemia, from a baseline value of 6.56 (3.0-14.9) to 3.86 (1.41-5.32), and restored to a value of 3.8 (2.8-12.1) min-1 after insulin challenge. This decrease in PS2/Ve is probably due to an increase in the brain glucose distribution volume induced by an insulin induced increased intracellular glucose uptake during the experiment. For phenylalanine (n = 5), PS1 was unchanged before, during, and after insulin challenge. In hyperinsulinemia, PS3/Ve for phenylalanine decreased in all subjects. We conclude that acutely elevated high plasma insulin levels in humans does not alter the brain uptake of glucose or phenylalanine from the blood. It seems, however, that high plasma insulin levels induce an increase in the movement of D-glucose and L-phenylalanine from the brain interstitial fluid into the intracellular compartment.

PEEP and low tidal volume ventilation reduce lung water in porcine pulmonary edema.

This study analyzed the effect of both positive end-expiratory pressure (PEEP) and reduction in tidal volume (VT) on extravascular lung water (EVLW) in a permeability model of pulmonary edema. Immediately after producing a pulmonary edema with oleic acid, 21 pigs were randomized into three groups. Group I (n = 8): PEEP of 0 cm H2O (ZEEP), VT of 12 ml/kg; Group II (n = 6): PEEP of 10 cm H2O, VT of 12 ml/kg; Group III (n = 7): PEEP of 10 cm H2O, VT of 6 ml/kg. EVLW was measured by the double indicator method (DI) at baseline (time 0) and after 30, 60, 120, 180, and 240 min and by the gravimetric method (G) at 240 min. Both methods correlated excellently (r = 0.94, p < 0.0001). EVLW-DI was significantly less with PEEP application (Group II versus Group I) at 180 min and thereafter. Likewise, EVLW-DI was less throughout the experimental period with reduced VT once PEEP was applied (Group III versus Group II). EVLW-G was less in Group II than in Group I at 16.3 +/- 2.7 and 23.2 +/- 4.2 ml/kg, respectively (p < 0.0001), and less in Group III than in Group II at 10.7 +/- 0.9 and 16.3 +/- 2.7 ml/kg (p < 0.0001). We conclude that early application of 10 cm H2O of PEEP reduces EVLW in permeability pulmonary edema. The lowering of VT reduced EVLW even further.

Transport of D-glucose and 2-fluorodeoxyglucose across the blood-brain barrier in humans.

The deoxyglucose method for calculation of regional cerebral glucose metabolism by PET using 18F-2-fluoro-2-deoxy-d-glucose (FDG) requires knowledge of the lumped constant, which corrects for differences in the blood-brain barrier (BBB) transport and phosphorylation of FDG and glucose. The BBB transport rates of FDG and glucose have not previously been determined in humans. In the present study these transport rates were measured with the intravenous double-indicator method in 24 healthy subjects during normoglycemia (5.2 +/- 0.7 mM). Nine subjects were restudied during moderate hypoglycemia (3.4 +/- 0.4 mM) and five subjects were studied once during hyperglycemia (15.0 +/- 0.7 mM). The global ratio between the unidirectional clearances of FDG and glucose (K1*/K1) was similar in normoglycemia (1.48 +/- 0.22), moderate hypoglycemia (1.41 +/- 0.23), and hyperglycemia (1.44 +/- 0.20). This ratio is comparable to what has been obtained in rats. We argue that the global ratio is constant throughout the brain and may be applied for the regional determination of LC. We also determined the transport parameters of the two hexoses from brain back to blood and, assuming symmetrical transport across the BBB, we found evidence of a larger initial distribution volume of FDG in brain (0.329 +/- 0.236) as compared with that of glucose (0.162 +/- 0.098, p < 0.005). The difference can be explained by the very short experimental time, in which FDG may distribute both intra- and extracellularly, whereas glucose remains in a volume comparable to the interstitial fluid of the brain.

Effects of Milrinone on Lung Water and Hemodynamics in Dogs with Oleic Acid Pulmonary Edema

The aim of this study was to investigate the effects of milrinone (MLN) on lung water and hemodynamics in dogs with oleic acid induced lung edema. Extravascular lung water volume (EVLWV) was measured as an index of lung water using a themo/sodium double indicator method. After baseline measurements, 0.08ml/kg of oleic acid was injected into the caval vein. Twelve mongrel dogs were divided into the following two groups; MLN group and control group (C). In the MLN group, 100μg/kg of MLN was administrated by bolus injection followed by infusion at 1.0μg/kg min. The same volume of saline was infused in to the C group. Values were again obtained at 30, 60 120, and 180 minutes after the start of MLN. EVLWV was significantly increased by oleic acid and was significantly reduced in the MLN group compared to the C group. Hypoxemia was improved by MLN. Pulmonary vascular resistance in the MLN group was significantly lower than that in the C group.

Blood‐brain barrier transport of amino acids in healthy controls and in patients with phenylketonuria

Blood-brain barrier permeability to phenylalanine and leucine in four patients with phenylketonuria and in four volunteers was measured five times by the double-indicator method at increasing plasma concentrations of phenylalanine. Based on the permeability-surface area product (PS) from blood to brain (PS1) and on plasma phenylalanine levels, Vmax and the apparent Km for phenylalanine were determined. Statistically significant relationships between plasma phenylalanine and PS1 were established in three out of four volunteers, the average Vmax value being 46.7 nmol/g per min and the apparent Km 0.328 mmol/L. Owing to saturation of the carrier, such a relationship could not be established in the patients. In phenylketonuria, PS1 for phenylalanine and leucine decreased significantly by 55% and 46%, respectively. Transport from brain back to blood, PS2, decreased significantly and cerebral large neutral amino acid net uptake was generally decreased in patients with phenylketonuria. In conclusion, the transport of L-phenylalanine across the human blood-brain barrier follows Michaelis-Menten kinetics. In phenylketonuria, brain permeability to large neutral amino acids is reduced by about 50% and net uptake appears decreased.