Degree Of Excess Research Articles

Preclinical Cushing's syndrome: report of seven cases and a review of the literature.

Adrenal adenomas showing autonomous cortisol secretion without specific endocrine symptoms are sometimes discovered in patients with adrenal incidentalomas. This entity has been described as subclinical or preclinical Cushing's syndrome (PCS), but the endocrine data of reported cases have varied and the diagnostic criteria of PCS have been uncertain. We report seven Japanese cases of PCS due to a unilateral, solitary adrenal adenoma with examination of the endocrine data of these patients. The diagnostic parameters of subtle hypercortisolism and the risk of postoperative adrenal insufficiency and surgical indications are discussed and reviewed. In the present cases, the most frequently found biochemical parameters of autonomous cortisol secretion were a low adrenocorticotropic hormone (ACTH) level (100%) and insufficient suppression of cortisol by low-dose dexamethasone (85.7%). Unilateral accumulation of radiopharmaceuticals in tumors was also frequently observed (100%). A postoperative hydrocortisone supplement was given to six of the seven patients for 5-122 days. It was not given to case 4, because a moderate response of 11-deoxycortisol to metyrapone was identified. Plasma ACTH levels and the diurnal rhythm of plasma cortisol rapidly recovered within 3 weeks postoperatively in six of the seven cases. This entity is heterogeneous and various degrees of cortisol excess have been observed. It should be diagnosed in the wide spectrum and the risk of adrenal insufficiency after surgery should be evaluated by dynamic tests such as the corticotropin-releasing hormone (CRH) test. Based on the results of the present study and a review of the literature, PCS patients may not require hydrocortisone supplement therapy for a long period.

Essential fatty acids in infant nutrition: lessons and limitations from animal studies in relation to studies on infant fatty acid requirements

Animal studies have been of pivotal importance in advancing knowledge of the metabolism and roles of n-6 and n-3 fatty acids and the effects of specific dietary intakes on membrane composition and related functions. Advantages of animal studies include the rigid control of fatty acid and other nutrient intakes and the degree, timing, and duration of deficiency or excess, the absence of confounding environmental and clinical variables, and the tissue analysis and testing procedures that cannot be performed in human studies. However, differences among species in nutrient requirements and metabolism and the severity and duration of the dietary treatment must be considered before extrapolating results to humans. Studies in rodents and nonhuman primates fed diets severely deficient in alpha-linolenic acid (18:3n-3) showed altered visual function and behavioral problems, and played a fundamental role by identifying neural systems that may be sensitive to dietary n-3 fatty acid intakes; this information has assisted researchers in planning clinical studies. However, whereas animal studies have focused mainly on 18:3n-3 deficiency, there is considerable clinical interest in docosahexaenoic acid (22:6n-3) and arachidonic acid (20:4n-6) supplementation. Information from animal studies suggests that brain and retinal concentrations of 22:6n-3 plateau with 18:3n-3 intakes of approximately 0.7% of energy, but this requirement is influenced by dietary 18:2n-6 intake. Blood and tissue concentrations of 22:6n-3 increase as 22:6n-3 intake increases, with adverse effects on growth and function at high intakes. Animal studies can provide important information on the mechanisms of both beneficial and adverse effects and the pathways of brain 22:6n-3 uptake.

ChemInform Abstract: Superior Performance of a Chiral Catalyst Confined within Mesoporous Silica.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Plasma very long chain fatty acids in 3,000 peroxisome disease patients and 29,000 controls.

The assay of plasma very long chain fatty acids (VLCFAs), developed in our laboratory in 1981, has become the most widely used procedure for the diagnosis of X-linked adrenoleukodystrophy (X-ALD) and other peroxisomal disorders. We present here our 17 years' experience with this assay. Three VLCFA parameters, the level of hexacosanoic acid (C26:0), the ratio of C26:0 to tetracosanoic acid (C24:0), and of C26:0 to docosanoic acid (C22:0), were measured in 1,097 males (hemizygotes) with X-ALD, 1,282 women heterozygous for this disorder, including 379 obligate heterozygotes, 797 patients with other peroxisomal disorders, and 29,600 control subjects. All X-ALD hemizygotes who had not previously received Lorenzo's oil or a diet with a high erucic acid content had increased VLCFA levels, but the application of a discriminant function based on all three measurements is required to avoid the serious consequences of a false-negative result. VLCFA levels are increased at day of birth, thus providing the potential for neonatal mass screening, are identical in the childhood and adult forms, and do not change with age. Eighty-five percent of obligate heterozygotes had abnormally high VLCFA levels, but a normal result does not exclude carrier status. VLCFA levels were increased in all patients homozygous for Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum's disease, and in patients with deficiencies of peroxisomal acyl-coenzyme A oxidase, bifunctional enzyme, and 3-oxoacyl-coenzyme A thiolase. In these patients the degree of VLCFA excess correlated with clinical severity.

Superior performance of a chiral catalyst confined within mesoporous silica

A chiral catalyst from the ligand 1,1′-bis(diphenylphosphino)ferrocene (dppf) anchored to the inner walls of the mesoporous support MCM-41 and co-ordinated to PdII has been shown to exhibit a degree of regioselectivity and enantiomeric excess, in the allylic amination of cinnamyl acetate, which is far superior to that of its homogeneous counterpart or that of a surface-bound analogue attached to a non-porous silica.

Subclinical Cushing's syndrome in adrenal incidentaloma.

Some patients with incidentally discovered adrenal adenomas display autonomous cortisol secretion not fully restrained by pituitary feedback, a condition that may be defined as subclinical Cushing's syndrome. We have evaluated the presence of subclinical Cushing's syndrome and its natural history in a cohort of patients with incidentally discovered adrenal adenomas. Fifty-three consecutive patients (30 women and 23 men; median age 58 years, range 18-81 years) were studied. Diagnostic procedures were initiated for extra-adrenal complaints. Patients with known extra-adrenal malignancies or patients with hypertension of possible endocrine origin were excluded. All patients underwent the following endocrine evaluation: (1) measurement of DHEA-S at 0800 h, (2) measurement of serum cortisol at 0800 and 2400 h, (3) measurement of the 24-h excretion of urinary free cortisol (UFC), (4) overnight low-dose dexamethasone suppression test, (5) measurement of plasma ACTH at 0800 h (mean of at least two samples on different days), (6) oCRH stimulation test. Different groups of healthy subjects recruited from the hospital medical staff and their relatives served as controls for the various tests. The same endocrine work-up was repeated after 12 months in 25 patients. All patients were followed up at regular intervals for at least 12 months with clinical examination and abdominal computed tomography. Subclinical hypercortisolism was arbitrarily defined as definitive, probable or possible, according to the degree of endocrine abnormalities. UFC was significantly higher in patients with incidentaloma than in controls (262, 25-690 nmol/24 h versus 165, 25-772 nmol/24 h; P = 0.012). The percentage of subjects who did not suppress on dexamethasone was greater among patients than among healthy subjects (9/53 (17%) versus 5/103 (5%), P = 0.026). Plasma ACTH concentrations were lower in patients with adrenal incidentaloma than in controls (3, 1-9 pmol/l versus 5, 1-14 pmol/l; P = 0.014). These findings consistently point toward a functional autonomy of the adrenal adenomas even if the degree of cortisol excess is mild. Three patients fulfilled the criteria for definitive subclinical hypercortisolism, five for probable and two possible, but none of them experienced clinical and/or biochemical progression to overt hypercortisolism after 12 months. During follow-up, no signs of extra-adrenal malignancy became manifest and the size of the mass did not increase significantly in any patient. This study provides a clear demonstration of the current opinion that some patients with incidentally discovered adrenal adenomas may be exposed to a subtle, silent hypercortisolism. In some patients, in whom the clustering of more abnormalities in the hypothalamo-pituitary-adrenal axis occurs, subclinical Cushing's syndrome could be assumed. This term should be preferred to that of pre-clinical Cushing's syndrome since the biochemical abnormalities do not become clinically manifest, at least in the short term.

Analysis of a lipase-catalyzed kinetic resolution by chiral normal-phase liquid chromatography.

As part of our investigation of structure-activity relationships in a Candida rugosa lipase-catalyzed ester hydrolysis reaction, methyl 2-(octylsulfinyl)benzoate has been studied, with respect to rate and enantioselectivity behaviour, using two different lipase preparations. A chiral normal-phase liquid chromatography method has been developed for determination of the experimental data, degree of conversion (c) and enantiomeric excess of the substrate (ees) or the product (eep), needed for calculation of the enantioselectivity in a kinetic resolution of this kind. A recently developed new class of network-polymeric chiral stationary phases, giving baseline-resolution with high selectivities for the ester substrates as well as their corresponding carboxylic acid products, permits, without any derivatization, an accurate and direct determination of the rate of the hydrolysis reaction and of the enantioselectivity from one and the same chromatogram.

Computer-aided modelling of stereoselective triglyceride hydrolysis catalyzed by Rhizopus oryzae lipase

Lipase from Rhizopus oryzae catalyzes the stereoselective hydrolysis of triglycerides and analogues. Stereopreference and degree of enantiomeric excess of the product varies with the structure of the substrate: trioctanoylglycerol (‘ester’) and the sn-2 analogues 2-X-1,3-dioctanoylpropandiol, where 2-X = 2- O-octyl (‘ether’) and 2-hexyl (‘alkane’), are preferentially hydrolyzed at sn-1, substitution by 2-phenyl (‘phenyl’) reverses the Stereopreference to sn-3. We have modelled the stereoselectivity of Rhizopus oryzae lipase by docking the tetrahedral intermediates of these substrates in two orientations, appropriate to hydrolysis at sn-1 or sn-3, respectively. The initial complexes were further relaxed by molecular dynamics simulations. The favoured orientation of a substrate is characterized by three factors: (1) The substrate fits well into the binding site. The glycerol backbone is relaxed and the sn-2 chain points to a well defined hydrophobic binding site. (2) The oxyanion is stabilized by an extra hydrogen bond from the side chain of Thr 83. (3) The substrate lacks repulsive interactions with protein side chains, especially of Leu 258. Our model is consistent with experimental data and explains qualitatively the ranking of four different substrates with regard to stereoselectivity. It can be used to design lipase mutants with modified stereoselectivity.

UTh isotope disequilibria and ocean island basalt generation in the Azores

A suite of 23 alkalic lavas from the Azores islands of Sao Jorge, Pico, Faial, Terceira and São Miguel have been analysed for their major and tram element and Sr, Nd, Pb and Th isotopic compositions. Previous studies have shown that lavas along the MAR show increases in La/Sm and 87Sr/ 86 Sr coupled with decreasing Fe towards the Azores platform inferred to reflect increasing dominance of a plume component over a depleted MORB-mantle component. The La/Sm and Sr, Nd and Pb isotope data of lavas from São Jorge, Pico, Faial and Terceira overlap the high La/Sm, 87Sr/ 86Sr end of the MAR lava array inferred to represent the deep seated plume and they have low Fe 8.0 ∗ compared with for example, Iceland basalts. When compared with the MAR array, higher Fe 8.0 ∗ and Na 8.0 and lower Si 8.0 probably reflect lower degrees of melting at higher average pressures beneath a lithospheric lid. The combination of enrichment in incompatible elements (including volatiles) with depletion in Fe in the regional plume component is a feature most likely to have developed within the lithospheric mantle. Lavas from São Miguel require an additional high 87Sr/ 86Sr, 207Pb/ 204Pb, low 143Nd/ 144Nd component with high Th/Nb which is suggested to result from incorporation of sediment in the source of these lavas. UTh isotope data indicate 9–29% 230Th excesses similar to those observed in alkalic basalts from Iceland or Hawaii. This, combined with the observation that lavas from Sao Miguel at the periphery of the inferred plume have smaller 230Th excesses (average 14%) than those nearer the centre, including the recent measurements from the MAR-ridge (average 23%), suggests that there is no simple correlation between buoyancy flux or lithospheric lid thickness and 230Th excesses. Long-term source Th/U ratios inferred from Pb isotopes are greater than those measured indicating U addition some time prior to partial melting. The large variations in ( 230Th/ 232Th) and ( 238U/ 232Th) are negatively correlated with 87Sr/ 86Sr indicating that much of the variation in U/Th reflects long-lived source heterogeneity. Moreover, the degree of 230Th excess is also negatively correlated with 87Sr/ 86Sr suggesting a link between melting process and source heterogeneity. The variations in 230Th excess are unlikely to result from thermally controlled variations in solidus pressure since this would require temperature differences (250°C) that are improbable at the length scale between São Miguel and Terceira (200 km). Instead, it is suggested that the incorporation of sediment and volatiles beneath São Miguel has led to increased rates of melting, resulting in smaller 230Th excesses, consistent with the higher volcanic output on Sao Miguel compared with Terceira.

Interdependence between degree of porphyrin excess and disease severity in congenital erythropoietic porphyria (Günther's disease).

Various clinical and biochemical observations point to a relationship between degree of disease expression and metabolic disturbance in autosomal recessive congenital erythropoietic porphyria (Günther's disease). Although the clinical manifestations have been well described since Günther's fundamental observations, an interdependence between disease severity and porphyrin excess has yet to be elucidated. We investigated porphyrin metabolism in nine Indian patients suffering from the characteristic clinical symptoms: skin photosensitivity, red-colored urine as a sign of extremely elevated porphyrinuria and mild to severe hemolytic anemia. Porphyrins in urine, feces and blood were analysed by HPTLC and HPLC in conjunction with spectrophotometry and spectrofluorometry. Uroporphyrinogen III synthase activities in red blood cells were determined using a coupled-enzyme assay. Biochemical studies revealed varying degrees of porphyrinuria with total urinary porphyrins between 23 and 102 mumol/24 h (normal < 0.2 mumol/24 h) and uroporphyrin predominance. Urinary and fecal coproporphyrin isomer I were markedly elevated to 87-97% and 81-93% (normal < 31%, < 75%), respectively. Overproduction of porphyrins led to a considerable porphyrinemia with mainly copro- and protoporphyrin. A hitherto undescribed fecal porphyrin pattern with increased protoporphyrin levels was found in three patients. This atypical finding was probably related to severe hemolysis since protoporphyrin can be excreted only via the liver with bile in the feces. High porphyrin levels in urine, feces and blood were associated with worse cutaneous symptoms. Activities of uroporphyrinogen III synthase in red blood cell lysates were decreased to between 9% and 30% of controls. Patients showed increased porphobilinogen deaminase activities, up to 190% of control. Deficiency of uroporphyrinogen III synthase activity was reflected by inversion of the relationship between and isomer III leading to dominance of isomer I. Elevation of porphobilinogen deaminase activities is related to hemolysis and, additionally, to regulatory compensation for the enzyme deficiency. Variations in both the severity of photosensitivity and the enhancement of porphyrin production and excretion indicate the molecular heterogeneity of this disease. These findings suggest a close relationship between the metabolic disturbance reflected by porphyrin excess and the severity of disease expression.

The 21-hydroxylase-deficient adrenal hyperplasias: More than ACTH oversecretion

Twenty-one hydroxylase (21-OH)-deficient classic adrenal hyperplasia (CAH) and nonclassic adrenal hyperplasia (NCAH) are two of the most common genetic disorders known to man, yet the mechanism(s) resulting in steroid excess remains unclear. Overactivation of the hypothalamic-pituitary-adrenal (HPA) axis and increased ACTH secretion appear to be important mechanisms resulting in steroid excess in untreated patients, at least in the classic forms of the disorder. Nonetheless, most NCAH patients do not demonstrate overactivity of the HPA axis. A few of these patients may demonstrate a mild degree of ACTH hyper-responsiveness to corticotropin-releasing hormone stimulation, and up to 40% have radiologic evidence of adrenocortical hyperplasia and/or isolated adenomas, suggesting that some degree of chronic ACTH excess is present. Another mechanism resulting in adrenocortical excess in adrenal hyperplasia, and primarily in NCAH, follows the alteration in enzyme kinetics resulting from the mutation of 21-OH. The mutated enzyme product is less efficient than the wild type, resulting in an increased precursor to product ratio, independent of ACTH levels. Hence, progesterone (P4) and 17-hydroxyprogesterone (17-HP) levels in these patients may remain above normal even in the presence of excess glucocorticoid administration. Overactivity of the renin-angiotensin system may also be important in stimulating adrenocortical steroidogenesis in patients with salt-wasting and in some with simple virilizing CAH. Alterations in ovarian and gonadotropic function, with the appearance of a polycystic ovary-like picture, also contribute to the androgen excess of these patients. Functional ovarian abnormalities in patients with CAH or NCAH may relate to a number of causes, including prenatal masculinization of the hypothalamic-pituitary-ovarian (HPO) axis by adrenal androgens, continued disruption of the HPO axis by persistently elevated P4 or androgen levels, and/or a direct glucocorticoid effect. Finally, these data suggest that the measurement of P4 or 17-HP may not be the most accurate marker of therapeutic efficacy, and suppression of both the ovaries and adrenals may be necessary for optimum steroidogenic control.

Hyperinsulinemia in postpubertal girls with a history of premature pubarche and functional ovarian hyperandrogenism.

Previous studies have documented the association of insulin resistance and hyperandrogenism in adult women with functional ovarian hyperandrogenism (FOH) or polycystic ovary syndrome (a form of FOH). However, the possible impact of adrenal hyperandrogenism development during childhood in premature pubarche (PP) patients on postpubertal insulin secretion patterns remains unclear. The fasting insulin to glucose ratio, C peptide, early insulin response to glucose (IRG), mean blood glucose, mean serum insulin (MSI), glucose uptake rate in peripheral tissues (M), and insulin sensitivity indexes (SI) in response to a standard oral glucose tolerance test were evaluated in 13 PP girls with FOH (group A; age, 17.2 +/- 0.5 yr), 11 eumenorrheic nonhirsute PP girls (group B; age, 16.6 +/- 0.5 yr), and 21 age-matched controls (group C). Body mass indexes (BMI) were similar in the 3 groups (group A, 23.3 +/- 0.8; group B, 22.5 +/- 0.6; group C, 20.6 +/- 0.5 kg/m2). MSI values were significantly higher in FOH patients than in controls (74.7 +/- 17.6 vs. 45.7 +/- 4.1 mU/L; P < 0.01), but were not different from those in group B (63.3 +/- 11.1 mU/L). Thirty-eight percent of FOH patients (group A) and 27% of non-FOH patients (group B), all of whom had normal BMI, showed MSI levels well above the upper normal limit for controls (> 83.3 mU/L). MSI correlated with the degree of ovarian hyperandrogenism [defined by an abnormal 17-hydroxyprogesterone response to challenge with the GnRH analog leuprolide acetate; group A] and with the free androgen index [testosterone (nanomoles per L)/sex hormone-binding globulin (nanomoles per L) x 100; groups A and B)]. Although IRG, glucose uptake rate in peripheral tissues, mean blood glucose, and SI values were not significantly different in the 3 groups, 3 patients in group A and 1 patient in group B showed decreased insulin sensitivity and/or an enhanced early IRG. Among others, significant correlations between MSI and free androgen index values (r = 0.6; P < 0.002; groups A and B) and between BMI and SI (r = -0.53; P < 0.05; groups A and B) were found. Peak 17-hydroxyprogesterone responses to ACTH at PP diagnosis correlated positively with SI in both groups of patients (r = 0.53; P < 0.007). Hyperinsulinemia is a common feature in adolescent PP patients with FOH and appears to be directly related to the degree of androgen excess. Long term follow-up of PP patients into adulthood is warranted to ascertain whether hyperinsulinemia actually precedes FOH development and whether overt insulin resistance ensues.

Th, Pb, Nd and Sr Isotope Variations in Volcanic Rocks from the Lesser Antilles

Th, Pb, Nd and Sr isotope data on Recent volcanic rocks from the Lesser Antilles arc provide constraints on melting processes and the relative contributions of various source components. Although many of the samples are close to U-Th equilibrium, the total range in (23~ is from 0.72 to 1.76 and (23Su/232Th) from 0.66 to 1.59 thus the data extend to both sides of the Th-U equiline (z3~ = 0.75-2.07), though Th excess predominates. There is no apparent correlation between the degree of disequilibrium, or U versus Th excess, and position from North (low-K tholeiitic) to South (calc-alkaline to s h o s h o n i t i c ) a l o n g the are. H o w e v e r , (23~ shows a broad negative correlation with S7Sr/S6Sr, 2~176 2~176 2~176 and is positively correlated with t43Nd/144Nd. The (23~ 87Sr/S6Sr and

Measurements of 10Be and 26Al production cross sections with 12 GeV protons by accelerator mass spectrometry.

The formation cross sections of $^{10}\mathrm{Be}$ and $^{26}\mathrm{Al}$ from Al, Fe, Co, Ni, Cu, Zn, Ag, and Au targets irradiated with 12 GeV protons were measured by accelerator mass spectrometry. The obtained cross sections were consistent with the excitation functions predicted from the literature values measured at other proton energies within the experimental uncertainties. The $^{10}\mathrm{Be}$ cross sections increased with an increase in the target mass. On the other hand, the $^{26}\mathrm{Al}$ cross sections decreased from Al to Ag targets, but increased somewhat from Ag to Au. The formation mechanisms of $^{10}\mathrm{Be}$ and $^{26}\mathrm{Al}$ including $^{7}\mathrm{Be}$, $^{22}\mathrm{Na}$, and $^{24}\mathrm{Na}$ are discussed with respect to fitting of the experimental results to the calculated values using the universal formula of Campi et al. During the course of the discussion, we introduce a new parameter, the degree of neuton excess (N-Z)/A, in order to classify light fragments more clearly.It is found that the production of $^{10}\mathrm{Be}$ and $^{24}\mathrm{Na}$ with positive values for the degree of neutron excess can be well reproduced by the formula, indicating that fragmentation is a dominant process for $^{10}\mathrm{Be}$ production from Fe to Au targets and for $^{24}\mathrm{Na}$ from Ag to Au. However, the values calculated by the formula overestimate the yields of $^{7}\mathrm{Be}$, $^{22}\mathrm{Na}$, and $^{26}\mathrm{Al}$ with negative values or zero for the neutron-excess parameter. Through a comparison of the calculated and experimental data it is also found that the cross section ratios of $^{10}\mathrm{Be}$${/}^{7}$Be, $^{24}\mathrm{Na}$${/}^{26}$Al, and $^{24}\mathrm{Na}$${/}^{22}$Na are linearly correlated with the degree of neutron excess of the targets. This suggests that the production of $^{7}\mathrm{Be}$, $^{22}\mathrm{Na}$, and $^{26}\mathrm{Al}$ with negative or zero (N-Z)/A by a fragmentation process from Ag to Au targets is suppressed relative to those of $^{10}\mathrm{Be}$ and $^{24}\mathrm{Na}$ with positive values of the neutron-excess parameter.

Plasma concentrations of calcitonin gene-related peptide in fluid overload

To investigate the hypothesis that calcitonin gene-related peptide (CGRP), a potent vasodilator, is an important physiological defence against fluid overload, plasma CGRP concentrations were measured in various degrees of fluid overload in 26 haemodialysis patients, for whom diuresis, mediated by atrial natriuretic peptide (ANP), is not a possible defence mechanism. Plasma CGRP concentrations were positively correlated with the degree of fluid excess (r = 0·815, p = 0·0001) and were significantly higher in 5 patients with severe fluid overload than in those less severely affected (143 [SE 14] vs 52 [11] pmol/l; p<0·001). CGRP may be an effective defence against complications of fluid overload since it can increase capitance by vasodilatation.

β-Thalassämie: Molekulare Pathogenese und klinische Variabilität

Clinically, homozygous beta-thalassaemia is characterised by a severe anaemia requiring regular transfusion therapy in most patients. However, there is a marked clinical variability ranging from this severe picture to the virtual absence of symptoms and haematological abnormalities. Biochemically, beta-globin synthesis in the erythroid precursors of the bone marrow is reduced or absent resulting in a relative excess of insoluble alpha-globin chains and dyserythropoiesis. The molecular genetics of this disorder is highly variable involving a multitude of different mutations of the beta-globin gene. These mutations can inactivate gene expression at all levels on its way from DNA to mature haemoglobin. The clinical picture is largely determined by the type of mutations inherited. Additionally the degree of alpha-globin chain excess can be influenced by the co-inheritance of alpha-thalassaemia or mutations resulting in the hereditary persistence of fetal globin synthesis (HPFH). This review discusses the relationship between the molecular defect and the clinical picture of patients with beta-thalassaemia.

A field study of hot water consumption in a modern hospital ward unit

A recent study into the requirements of hot water services for a modern hospital ward unit quantifies the degree of excess that existing guidelines in the UK provide and explains how this situation has evolved. D.R. Corless, Energy Efficiency Engineer of the University of Manchester, suggests that a review of guidelines is long overdue.

Hypertension Profiling by Total Body Water (Tbw) Determinations in Patients on Chronic Hemodialysis

Hypertension is an important risk factor in hemodialysis patients. Fluid overload and increased peripheral resistance are considered the two main causes. We studied the relation between volume state and blood pressure in 18 hemodialysis patients. Actual total body water (aTBW) was measured as tritium space and "ideal" total body water (iTBW) by an anthropometric method. The difference between aTBW and iTBW was considered a measure of fluid excess or deficit. Twelve patients were overhydrated, 5%-23%. Their predialysis blood pressure was significantly correlated to their degree of fluid excess; systolic BP:r = 0.71, p = 0.03, diastolic BP:r = 0.73, p = 0.02, mean arterial BP:r = 0.76, p = 0.03. Five of these patients had multiple antihypertensive drugs instead of adequate ultrafiltration. Five patients had a fluid deficit of -3 to -13% and hypertension due to vasoconstriction. Four of these were adequately treated with antihypertensive drugs but had exaggerated ultrafiltration. TBW determination with tritium is simple to perform and gives information on the volume state and thereby on the cause of hypertension in hemodialysis patients. Based on this, appropriate treatment can be chosen.

Stereochemisty of oxygenation of organic sulphides with pig liver microsomal FAD-containing mono-oxygenase: comparison with cytochrome P-450PB oxidations

The enantiotopic differentiating ability of pig liver microsomal FAD-containing mono-oxygenase (EC 1.14.13.8) in the oxygenation of nine unsymmetrical sulphides has been investigated. By this enzymatic oxygenation, the sulphides are converted into the corresponding optically active sulphoxides with varying degrees of enantiomeric excess (96–12%).Three cyclic sulphides have been studied in order to establish the diastereotopic differentiating ability of the enzyme. In the oxygenation of racemic 2-methyl-2,3-dihydrobenzo[b]thiophene both enantiomeric and diastereotopic differentiation appears to take place concurrently with high selectivity. The enantiotopic, diastereotopic, and enantiomeric differentiating abilities of the FAD-containing mono-oxygenase are all higher than those of the phenobarbital-induced rabbit liver microsomal cytochrome P-450.

Alteration of the nucleotide-binding site asymmetry of chloroplast coupling factor 1 by catalysis.

Fluorescence resonance energy transfer was used to show that ATP hydrolysis induces a change in the properties of two nucleotide-binding sites in isolated chloroplast coupling factor 1 (CF1). The fluorescence donor was Lucifer Yellow vinyl sulfone (4-amino-N-[3-(vinylsulfonyl)phenyl]naphthalimide- 3,6-disulfonate), covalently bound to a unique site on the alpha subunit between nucleotide-binding sites 2 and 3. The fluorescence acceptor was the ATP analog 2'(3')-trinitrophenyladenosine 5'-triphosphate (TNP-ATP), incorporated specifically into nucleotide-binding site 1. Energy transfer from Lucifer Yellow to TNP-ATP in site 1 was greater if catalysis occurred before TNP-ATP was incorporated than if no catalysis occurred, indicating that one of the nucleotide-binding sites near the Lucifer Yellow had changed its properties to those of site 1 as a result of catalysis. The amount of energy transfer increased with the degree of substrate excess during catalysis, as expected if catalysis were required for the new site 1 location. ADP, which binds to CF1, but is not a substrate for hydrolysis, caused little energy transfer. Titration of site 3 with TNP-ATP showed greater energy transfer from Lucifer Yellow when catalysis had not occurred, indicating that sites 1 and 3 switched properties as a result of catalysis. The amount of energy transfer declined exponentially with time between removal of substrate and addition of TNP-ATP to site 1, with a half-time of 1.5-2 h at room temperature. This result suggests that the change that results in switching of nucleotide-binding sites 1 and 3 relaxes in the absence of substrate. Our results show that the asymmetry of the nucleotide-binding sites of CF1 is not a permanent feature of the molecule.