Electrolysis-enhanced anaerobic digestion of wastewater.

This study demonstrates enhanced methane production from wastewater in laboratory-scale anaerobic reactors equipped with electrodes for water electrolysis. The electrodes were installed in the reactor sludge bed and a voltage of 2.8-3.5 V was applied resulting in a continuous supply of oxygen and hydrogen. The oxygen created micro-aerobic conditions, which facilitated hydrolysis of synthetic wastewater and reduced the release of hydrogen sulfide to the biogas. A portion of the hydrogen produced electrolytically escaped to the biogas improving its combustion properties, while another part was converted to methane by hydrogenotrophic methanogens, increasing the net methane production. The presence of oxygen in the biogas was minimized by limiting the applied voltage. At a volumetric energy consumption of 0.2-0.3 Wh/L(R), successful treatment of both low and high strength synthetic wastewaters was demonstrated. Methane production was increased by 10-25% and reactor stability was improved in comparison to a conventional anaerobic reactor.

Methane production in an UASB reactor operated under periodic mesophilic-thermophilic conditions.

Methane production was studied in a laboratory-scale 10 L anaerobic upflow sludge bed (UASB) reactor with periodic variations of the reactor temperature. On a daily basis the temperature was varied between 35 and 45 degrees C or 35 and 55 degrees C with a heating period of 6 h. Each temperature increase was accompanied by an increase in methane production and a decrease in the concentration of soluble organic matter in the effluent. In comparison to a reactor operated at 35 degrees C, a net increase in methane production of up to 22% was observed. Batch activity tests demonstrated a tolerance of mesophilic methanogenic populations to short-term, 2-6 h, temperature increases, although activity of acetoclastic methanogens decreased after 6 h exposure to a temperature of 55 degrees C. 16S sequencing of DGGE bands revealed proliferation of temperature-tolerant Methanospirillum hungatii sp. in the reactor.

The role of complement in immunological demyelination of the mammalian spinal cord.

STUDY DESIGN: Specificity of serum complement component to elicit immunological demyelination. OBJECTIVES: To assess the role of complement components and pathways in experimental immunological demyelination of the adult rat spinal cord. SETTING: ICORD, University of British Columbia, Vancouver, Canada. SUBJECTS: We used 32 adult male Sprague-Dawley rats, of approximately 220 g weight. METHODS: Rats received intraspinal infusions of demyelinating reagents, delivered by osmotic minipump, for a 7-day infusion at 0.5 microl/h. Reagents consisted of a polyclonal antibody to galactocerebroside and human serum complement. Complement sera deficient for a single component were used to assess the role of the alternative pathway, the classical pathway, and the membrane attack complex. Demyelination was assessed, at 7 days, ultrastructurally. RESULTS: Removal of C3 protein, common to classical and alternative complement pathways, or C4 protein, a classical pathway protein, resulted in no demyelination. However, complement deficient in Factor B, an alternative pathway protein, produced effective demyelination. Upon removal of C5 or C6, membrane attack complex proteins, demyelination was also observed. CONCLUSION: This suggests that the classical pathway is sufficient for the protocol to demyelinate the adult rat spinal cord, and that the membrane attack complex is also not required.

Occurrence of Proteocephalus tetrastomus (Rudolphi, 1810) (Cestoda: Proteocephalidea) in larval rainbow smelt (Osmerus mordax) in North America: identification of a potential pathogen confirmed.

A morphological evaluation and genetic analysis (sequencing of ITS2 region of rDNA) of proteocephalidean cestodes from rainbow smelt (Osmerus mordax) in the Saint Lawrence Estuary, Canada, has shown their conspecificity with Proteocephalus tetrastomus, a specific parasite of smelt (Osmeridae), previously known only from northern Europe, Russia, and Japan. The parasite occurs only in larval, but not adult, smelt in the Saint Lawrence Estuary. Prevalence of larval smelt infection was 42% (n = 50), mean intensity 2.1 +/- 2.4 and mean abundance 1.1 +/- 1.0.

Use of an alpha-glucosidase inhibitor to maintain glucose homoeostasis during postprandial exercise in intensively treated Type 1 diabetic subjects.

AIM: We evaluated the effects of an alpha-glucosidase inhibitor, acarbose, on glucose homoeostasis during postprandial exercise in Type 1 diabetic subjects. METHODS: Seven Type 1 diabetic subjects with good glycaemic control on ultralente-regular insulin were randomized in a single blind cross-over study to acarbose 100 mg or placebo taken with a mixed meal (600 kcal, 75 g carbohydrates), followed 90 min later by 30 min of exercise at 50% maximum aerobic capacity. Glucose turnover was measured by tracer (d-[6,6,2H2]glucose) methodology, and intestinal glucose absorption was quantified using carbohydrate polymers labelled with [13C]glucose. RESULTS: Acarbose resulted in a significant decrease in the postprandial glycaemic rise (mean +/- SEM 2.9 +/- 0.6 vs. 5.0 +/- 0.7 mmol/l; P < 0.005) and in the glycaemic nadir during exercise (- 0.8 +/- 0.6 vs. 0.9 +/- 1.3 mmol/l below baseline; P < 0.05). Total glucose appearance increased similarly under the two treatments during the postprandial (27.0 vs. 27.9 micromol per kg per min) and exercise (33.9 vs. 33.5 micromol per kg per min) periods. Mean glucose absorption was significantly delayed by acarbose (7.8 vs. 10.2 micromol per kg per min; P < 0.02), but was compensated by the lack of postprandial suppression of hepatic glucose production (106% of basal hepatic glucose production vs. 81%; P < 0.006). Episodes of hypoglycaemia were no different (three vs. six). CONCLUSION: These results indicate that, in Type 1 diabetic subjects, acarbose results in a better glycaemic profile during postprandial exercise and suggest that it could lead to a lower risk of exercise-induced hypoglycaemia due to delayed glucose absorption and less suppression of hepatic glucose production.

Guidelines for premeal insulin dose reduction for postprandial exercise of different intensities and durations in type 1 diabetic subjects treated intensively with a basal-bolus insulin regimen (ultralente-lispro).

OBJECTIVE: To evaluate and validate appropriate premeal insulin dose reductions for postprandial exercises of different intensities and durations to minimize the risk of exercise-induced hypoglycemia in type 1 diabetic subjects. RESEARCH DESIGN AND METHODS: Eight male type 1 diabetic patients on a basal-bolus insulin regimen of ultralente (UL) as basal insulin and lispro (LP) as premeal insulin were tested in a randomized, crossover fashion during postprandial exercise at 25% VO2max for 60 min, 50% VO2max for 30 and 60 min, and 75% VOmax for 30 min starting 90 min after a standardized mixed breakfast (600 kcal, 75 g carbohydrates). Each subject served as his own control and was rested after a full dose of insulin LP (LP 100%) and/or 50% (LP 50%) and/or 25% (LP 25%) of the current dose. RESULTS: At all intensities, the full premeal insulin dose was associated with an increased risk of hypoglycemia. At 25% VO2max for 60 min, a 50% reduction in the premeal insulin dose resulted in plasma glucose of -0.62 mmol/l compared with baseline at the end of exercise. At 50% VO2max for 30 and 60 min, 50 and 75% reductions of the premeal insulin dose were associated with plasma glucose of -0.39 and +0.49 mmol/l, respectively, at the end of the exercise. At 75% VO2max, a 75% reduction of the premeal insulin dose was required to achieve appropriate postexercise plasma glucose (+0.71 mmol/l). Such reductions in the premeal insulin dose resulted in a 75% decrease in the incidence of exercise-induced hypoglycemia. CONCLUSIONS In well-controlled type 1 diabetic subjects on intensive insulin therapy with the basal-bolus (UL-LP) insulin regimen, risk of hypoglycemia can be minimized during postprandial exercises of different intensities and different durations by appropriate reduction of premeal insulin LP.

Model for focal demyelination of the spinal dorsal columns of transgenic MBP-LacZ mice by phototargeted ablation of oligodendrocytes.

Focal demyelination models provide powerful tools to study demyelination and remyelination in the central nervous system. In this report, we present a novel technique, which selectively targets oligodendrocytes within the spinal cord of transgenic mice to produce focal demyelination. Transgenic mice expressing the E. coli LacZ (beta-galactosidase) gene from the myelin basic protein promotor allowed for oligodendrocyte-specific cleavage of topically applied fluorescein-di-beta-galactopyranoside liberating photoactivatable fluorescein. Subsequent fluorescence illumination generated oxygen radicals that oxidized a second exogenous substrate, 3-amino-9-ethyl carbazole, to form a toxic precipitate within oligodendrocytes. Histochemical staining of the spinal cord dorsal columns 8 days following phototargeting revealed that the treated region no longer contained beta-galactosidase-positive cells. Focal demyelination of the dorsal columns was observed to a depth of 150 microm in transverse semithin plastic sections. Numerous bundles of naked axons interspersed with myelin, debris-laden macrophages, and reactive astrocytes were evident by electron microscopy. Remyelination of axons by both oligodendrocytes and invading Schwann cells was observed within the treated region 14 days after phototargeting. Newly generated oligodendrocytes were identified within the demyelinated region by their incorporation of bromodeoxyuridine. Thus, this novel focal demyelination protocol provides: (1) a method for selective targeted ablation of oligodendrocytes in vivo, (2) control over the extent of the demyelinated region, with (3) an environment that maintains its remyelination capacity. Phototargeted ablation of oligodendrocytes may therefore be a useful model for studying axon-glia interactions, axon regeneration within a demyelinated zone, and remyelination of axons.

Increased hepatic glucose production response to glucagon in trained subjects.

This study was designed to characterize the impact of endurance training on the hepatic response to glucagon. We measured the effect of glucagon on hepatic glucose production (HGP) in resting trained (n = 8) and untrained (n = 8) healthy male subjects (maximal rate of O2 consumption: 65.9 +/- 1.6 vs. 46.8 +/- 0.6 ml O2.kg-1.min-1, respectively, P < 0.001). Endogenous insulin and glucagon were suppressed by somatostatin (somatotropin release-inhibiting hormone) infusion (450 micrograms/h) over 4 h. Insulin (0.15 mU.kg-1.min-1) was infused throughout the study, and glucagon (1.5 ng.kg-1.min-1) was infused over the last 2 h. During the latter period, plasma glucagon and insulin remained constant at 138.2 +/- 3.1 vs. 145.3 +/- 2.1 ng/l and at 95.5 +/- 4.5 vs. 96.2 +/- 1.9 pmol/l in trained and untrained subjects, respectively. Plasma glucose increased and peaked at 11.4 +/- 1.1 mmol/l in trained subjects and at 8.9 +/- 0.8 mmol/l in untrained subjects (P < 0.001). During glucagon stimulation, the mean increase in HGP area under the curve was 15.8 +/- 2.8 mol.kg-1.min-1 in trained subjects compared with 7.4 +/- 1.6 mol.kg-1.min-1 in untrained subjects (P < 0.01) over the first hour and declined to 6.8 +/- 2.8 and 4.9 +/- 1.4 mol.kg-1.min-1 during the second hour. In conclusion, these observations indicate that endurance training is associated with an increase in HGP in response to physiological levels of glucagon, thus suggesting an increase in hepatic glucagon sensitivity.

Regeneration of brainstem-spinal axons after lesion and immunological disruption of myelin in adult rat.

We previously observed that the transient developmental suppression of myelination or disruption of mature myelin, by local intraspinal infusion of serum complement proteins along with a complement-fixing, myelin-specific antibody (e.g., anti-Galactocerebroside), facilitated avian brainstem-spinal axonal regeneration after spinal transection. We now report the effects of similar immunological protocols on axonal regeneration in the injured adult rat spinal cord. After a lateral hemisection injury of the T10 spinal cord, infusion of the above reagents, over 14 days at T11, facilitated the regeneration of some brainstem-spinal axons. The hemisection lesion enabled comparisons between the retrograde labeling within an injured brainstem-spinal nucleus and the uninjured contralateral homologue. The brainstem-spinal nucleus examined in detail was the red nucleus (RN), chosen for its relatively compact descending pathway within the dorsolateral cord. Comparing the number of labeled neurons within each RN, of an experimentally myelin suppressed animal, indicated that approximately 32% of injured rubrospinal projections had regenerated into the caudal lumbar cord. In contrast, control-treated animals (e.g., PBS vehicle alone, GalC antibody alone, or serum complement alone) showed little or no axonal regeneration. We also examined the ultrastructural appearance of the treated cords. We noted demyelination over 1-2 segments surrounding the infusion site (T11) and a further two segments of myelin disruption (delamination) on either side of the demyelinated zone. The demyelination is an active process (< 3 days) with microglia and/or macrophages engulfing myelin. Thus, the facilitation of axonal regeneration through the transient suppression of CNS myelin may be fundamental to all higher vertebrates.

Glucose turnover and gluconeogenesis during pregnancy in women with and without insulin-dependent diabetes mellitus.

OBJECTIVE: To characterize the effect of pregnancy on glucose turnover and gluconeogenesis in healthy women and in women with well-controlled insulin-dependent diabetes mellitus (IDDM). DESIGN: Prospective clinical study. SETTING: Clinical research unit of the Hôtel-Dieu de Montréal hospital. PARTICIPANTS: Five healthy pregnant women and 6 pregnant women with IDDM. INTERVENTIONS: Glucose turnover and gluconeogenesis in the postabsorptive state at 16 and 32 weeks' gestation and at 24 weeks postpartum were studied with the use of a double stable isotope technique (D[2,3,4,6,6(2)H]-glucose and L[1,2,3(13)C]-alanine). In the women with IDDM, plasma glucose levels were controlled by continuous subcutaneous insulin infusion throughout pregnancy and with a Biostator on the morning of the study. RESULTS: In the women without IDDM, hepatic glucose production was 11.6 (standard error of the mean [SEM] 2.2) mumol/kg per minute at 16 weeks' gestation, 12.5 (SEM 1.8) mumol/kg per minute at 32 weeks' gestation, and 13.2 (SEM 1.9) mumol/kg per minute at 24 weeks postpartum. In the women with IDDM, it was 10.7 (SEM 2.4) mumol/kg per minute, 10.5 (SEM 1.2) mumol/kg per minute and 12.3 (SEM 0.5) mumol/kg per minute at the same respective periods. The difference in levels between the 2 groups was not significant. Levels of the gluconeogenic precursors alanine and lactate were increased during pregnancy in both the women without IDDM (from 0.18 [SEM 0.02] mmol/L and 0.64 [SEM 0.09] mmol/L, respectively, to 0.25 [SEM 0.02] mmol/L and 1.15 [SEM 0.17] mmol/L, respectively, p < 0.01) and in those with IDDM (from 0.15 [SEM 0.01] mmol/L and 0.47 [SEM 0.04] mmol/L, respectively, to 0.19 [SEM 0.02] mmol/L and 0.70 [SEM 0.01] mmol/L, respectively, p < 0.05). After an overnight fast, gluconeogenesis from alanine was not affected by pregnancy in both groups of women. In the women without IDDM, the plasma insulin level was low in early pregnancy (33.6 [SEM 3.6] pmol/L) and increased in late gestation (87.6 [SEM 9.6] pmol/L) compared with postpartum levels (60.0 [SEM 7.8] pmol/L). Plasma glucagon levels tended to rise in late gestation (from 95.1 [SEM 6.7] ng/L to 116.0 [SEM 36.0] ng/L). In the women with IDDM, the free plasma insulin and plasma glucagon levels were higher in early pregnancy (55.2 [SEM 6.6] pmol/L and 196.1 [SEM 29.8] ng/L, respectively) and did not change significantly during pregnancy. CONCLUSION: Basal glucose turnover and gluconeogenesis are not increased during pregnancy in women without IDDM or in women with well-controlled IDDM. The decrease in the plasma glucose level during pregnancy suggests that the use of glucose by the growing fetus is augmented and that this is not totally compensated for by a rise in postabsorptive hepatic glucose production. The glucose requirement by the growing fetus is probably supplied by the increased postprandial plasma glucose level.

Fluoxetine improves insulin sensitivity in obese patients with non-insulin-dependent diabetes mellitus independently of weight loss.

OBJECTIVE: To study the effect of fluoxetine, a specific serotonin reuptake inhibitor, on insulin sensitivity in obese patients with non-insulin-dependent diabetes mellitus (NIDDM) independently of its action on body weight. RESEARCH DESIGN AND METHODS: In a randomized, double-blind, placebo-controlled trial, insulin-mediated glucose disposal was measured in 12 obese patients with NIDDM on diet alone before and after four weeks of treatment with either placebo (n = 6) or fluoxetine (n = 6) at a dose level of 60 mg once a day. Insulin-mediated glucose disposal was assessed by the 2-step euglycemic hyperinsulinemic clamp technique. Patients were instructed on a weight-maintaining diet. RESULTS: Insulin infusion at 40 mU.m-2.min-1 resulted in insulin levels of 720 +/- 70 pmol. L-1 with a mean plasma glucose value of 6.4 +/- 0.2 mmol. L-1. Compared to placebo, fluoxetine increased glucose disposal (M) by 2.4-fold (P < 0.05), the insulin sensitivity index (M/I) by 2.7-fold (P < 0.03) and the glucose metabolic clearance rate (MCR) by 2.9-fold (P < 0.03). Insulin infusion at 400 mU.m-2. min-1 elicited insulin levels of 12947 +/- 1512 pmol. L-1 with a mean plasma glucose value of 5.6 +/- 0.4 mmol. L-1. Compared to placebo, fluoxetine increased M by 30% (P = NS), M/I by 40% (P < 0.04) and MCR by 23% (P < 0.04). Patient weight remained stable throughout the study with no change in dietary intake. CONCLUSION: Fluoxetine improves insulin-mediated glucose disposal in obese patients with NIDDM independently of weight loss.

Glucose metabolism during exercise in man: the role of insulin and glucagon in the regulation of hepatic glucose production and gluconeogenesis.

This study was designed to further characterize the role of insulin and glucagon in the regulation of glucose production and gluconeogenesis during a 2-h mild intensity exercise (40% VO2max) in 14 h fasted healthy male subjects. Endogenous insulin and glucagon secretions were suppressed by the infusion of somatostatin. The pancreatic hormones were replaced singly or in combination to match the hormonal concentrations observed during exercise in control subjects. Glucose turnover was determined by a tracer method using the stable isotope D-[2,3,4,6,6-2H]glucose. Gluconeogenesis was estimated by the simultaneous infusion of L-[1,2,3-13C]alanine to follow the conversion of alanine to glucose. Hepatic glucose production significantly increased from a resting rate of 12.1 +/- 0.2 to 27.6 +/- 1.4 mumol.kg-1.min-1 during exercise (p < 0.05). In the absence of glucagon, this increase in hepatic glucose production during exercise was totally abolished (p < 0.05). When insulin was made deficient, in the presence of glucagon, there was an overshoot in the increase in hepatic glucose production during exercise to 36.4 +/- 1.6 mumol.kg-1.min-1 (p < 0.05). The normal increase in hepatic glucose output during exercise was reproduced when both insulin and glucagon were replaced. Exercise increased gluconeogenesis by 47% above the resting level (p < 0.05). When glucagon was made deficient, in the absence or presence of insulin, this increase in gluconeogenesis was totally suppressed (p < 0.05). Furthermore, glucagon replacement during exercise in the absence of insulin resulted in a further increase in gluconeogenesis to 93% above resting value (p < 0.05). From these observations, it is concluded that during prolonged mild intensity exercise in healthy subjects, the rise in glucagon is essential for the increase in hepatic glucose production and the increase in gluconeogenesis. It is also suggested that the lower level of insulin during exercise still exerts a restraining effect on glucagon-stimulated glucose production and gluconeogenesis, thus preventing hyperglycemia.

Glucose metabolism during exercise in man: the role of insulin in the regulation of glucose utilization.

The present study was designed to characterize further the role of insulin in the regulation of glucose utilization during a 2-h exercise at 40% VO2max in 14 h fasted, healthy subjects. Endogenous insulin and glucagon were suppressed by somatostatin infusion and replaced singly or in combination to match the hormonal concentrations observed during similar exercise in saline-treated control subjects. Glucose kinetics were determined by a tracer method using D-[2,3,4,6,6-2H]glucose. In the exercising controls, during the last hour of the exercise, plasma glucose remained stable (4.26 +/- 0.06 mmol/L) and glucose utilization (Rd) increased significantly (p < 0.05) from 12.2 +/- 0.2 to 28.6 +/- 1.3 mumol.kg-1.min-1. During insulin deficiency without glucagon replacement, plasma glucose was maintained at 3.74 +/- 0.10 mmol/L by dextrose infusion, but with glucagon replacement plasma glucose increased to 6.69 +/- 0.24 mmol/L (p < 0.05). These hormonal changes were associated with an increase in Rd to 18.6 +/- 1.1 mumol.kg-1.min-1 (p = ns versus resting controls) and to 37.9 +/- 1.9 mumol.kg-1.min-1 (p < 0.05 versus resting controls), respectively. When insulin was replaced without glucagon replacement, plasma glucose was maintained at 3.85 +/- 0.06 mmol/L by dextrose infusion and Rd increased significantly (p < 0.05) from the resting value to 25.9 +/- 0.7 mumol.kg-1.min-1. When insulin was replaced together with glucagon, the plasma glucose (4.29 +/- 0.15 mmol/L) and the Rd (32.1 +/- 0.9 mumol.kg-1.min-1, p < 0.05 versus the resting value) obtained were similar to the values from the saline exercising control. Glucose metabolic clearance rate (MCR) significantly increased (p < 0.05) during exercise in all protocols. When insulin was made deficient, MCR increased 2-fold (p < 0.05) during exercise (2.7 to 4.8 and 5.4 mL.kg-1.min-1, respectively, with and without glucagon deficiency). However, when insulin was present, with and without glucagon deficiency, it increased further to 6.7 and 7.5 mL.kg-1.min-1, respectively, and values were different (p < 0.05) from glucose MCRs during insulin deficiencies. It is concluded that in 14 h fasted, healthy subjects, exercise per se can stimulate whole body glucose uptake even when insulin is made deficient. Insulin is necessary, however, for optimal glucose utilization during prolonged mild intensity exercise.

Targeting of glucose transport proteins for tumor imaging: is it feasible?

UNLABELLED: If glucose transport proteins (Glut) are elevated in tumors they may be good targets for tumor imaging. For targeting, the overexpression of Glut should be a general characteristic of tumors. Moreover agents which bind to Glut should accumulate selectively in tumors. METHODS: To test this, we quantitated Glut in isolated membranes from three human tumor xenografts, two murine tumor models and normal murine tissues using direct binding studies. Additionally, the biodistribution of two compounds which bind to Glut, 7-[[(2-(3-(125I-p-hydroxyphenyl)propionyl)aminoethyl)amino]carbonyl]-7-+ ++desacetyl-forskolin([125I]HPP forskolin) and [3H]cytochalasin B, were studied in a tumor model which overexpressed Glut. RESULTS: There were multiple classes of binding sites for [3H]cytochalasin B and a percentage of these sites were competitive with D-glucose but not L-glucose. The rank potency and IC50 values for [3H]cytochalasin B binding were: 2-deoxy-D-glucose (4.5 mM) > or = D-glucose (7 mM) > mannose (25 mM) > galactose (35 mM) > rhamnose (1-3 mM) > sorbitol (1-3 mM) and were similar to reported values for transport. The average density of Glut in four tumor models and normal tissues was between 0.7 and 4 pmole/mg protein, but Kd values were not significantly different (69 nM). In LX-1 human lung tumor xenograft (LX-1) Glut were 10-to-20-fold higher than other tissues (21.6 +/- 0.6 pmole/mg protein, p<0.01). Immunostaining of Glut-1 was more prominent in LX-1 than other xenograft tumors, consistent with the binding data. Glut density was highest in poorly vascularized regions suggesting that Glut upregulation was related to a biofeedback mediated event. Iodine-125 HPP-forskolin and [3H]cytochalasin B did not localize in LX-1 tumors. CONCLUSION: Glut overexpression was not a common characteristic of the five tumors tested. Iodine-125 HPP-forskolin and [3H]cytochalasin B did not localize in LX-1 tumors, indicating that these agents did not target tumors with upregulated Glut. Results suggest that Glut are not a promising target for tumor imaging.

Labeling cyclic glycoprotein IIb/IIIa receptor antagonists with 99mTc by the preformed chelate approach: effects of chelators on properties of [99mTc]chelator-peptide conjugates.

Several cyclic GPIIb/IIIa receptor antagonists were labeled with 99mTc by the preformed chelate approach using chelators such as H4L1 [4,5-bis(mercaptoacetamido)pentanoic acid], H4L2 [3,4-bis-(mercaptoacetamido)benzoic acid], H3L3 [2-(mercapto)ethylaminoacetyl-L-cysteine], H4L4 [N-(mercaptoacetyl)glycylglycylglycine], H4L5 [N-[2-(mercapto)propionyl]glycylglycylglycine], and H4L6 [N-[2-(mercapto)propionyl]glycylglycyl-gamma-aminobutyric acid]. In this approach, the [99mTc]chelator complexes are formed first, followed by the activation of the carboxylic group on the complex by formation of its tetrafluorophenol (TFP) ester and the conjugation of the TFP ester with an amino group of a cyclic GPIIb/IIIa receptor antagonist. The 99mTc-labeled cyclic GPIIb/IIIa receptor antagonists were characterized by radio-HPLC (high-performance liquid chromatography); differences in lipophilicity of the [99mTc]chelator-peptide conjugate are attributable to the effects of both the cyclic peptide and the chelator.

Glucose homeostasis during spontaneous labor in normal human pregnancy.

Using stable isotope, glucose turnover was measured in six normal pregnant women during the various stages of labor; during the latent (A1) and active (A2) phases of cervical dilatation, during fetal expulsion (B), and during placental expulsion (C). These data were compared to measurements made in five postpartum women. Pancreatic hormones and cortisol were also measured. In four other normal women undergoing spontaneous labor, catecholamines and free fatty acids were measured. Plasma glucose increased throughout labor from 4.0 +/- 0.2 (A1) to 5.5 +/- 0.5 mmol/L (C) (P < 0.01), compared to 4.7 +/- 0.1 in the postpartum women. Glucose utilization and production were increased throughout labor at 33.4 +/- 3.1 and 32.8 +/- 3.1 mumol/kg min, respectively, compared to 8.2 +/- 0.9 in postpartum women. Glucose metabolic clearance was also increased to 7.5 +/- 0.8 mL/kg.min compared to that in nonpregnant women (1.8 +/- 0.3). Plasma insulin remained at 59 +/- 5 pmol/L during stages A1, A2, and B, but increased to 115 +/- 15 pmol/L during stage C. Plasma glucagon was increased throughout labor at 127 +/- 7 pg/mL, compared to 90 +/- 4 pg/mL in control postpartum women. Plasma cortisol increased during labor from 921 +/- 136 to 2018 +/- 160 nmol/L, compared to 645 +/- 355 during the postpartum period. Epinephrine and norepinephrine also increased during labor from 218 +/- 132 pmol/L and 1.09 +/- 0.16 nmol/L to 1119 +/- 158 and 3.61 +/- 1.04, respectively. It is concluded that labor is associated with a marked increase in glucose utilization and production. These findings suggest that muscle contraction (uterus and skeletal) independent of insulin is a major regulator of glucose utilization during labor. Furthermore, the increase in hepatic glucose production could be favored by an increase in glucagon, catecholamines, and cortisol.

Antisense suppression of S-RNase expression in Nicotiana using RNA polymerase II- and III-transcribed gene constructs.

In the Solanaceae, self-incompatibility is controlled by a single, multi-allelic ('S') locus. One product of this locus is a ribonuclease, the S-RNase, which is expressed predominantly in mature pistils and has recently been shown to cause allele-specific pollen rejection in transgenic plants. Hybrid Nicotiana plumbaginifolia x N. alata plants were used to test the effects of antisense suppression of the SA2-RNase from N. alata using three different gene constructs: two driven by RNA polymerase II-transcribed promoters, and the third, containing a truncated soybean tRNA (met-i) gene, transcribed by RNA polymerase III. All three constructs caused suppression of S-RNase activity in the transgenic plants. Unexpectedly, the CaMV 35S promoter was more effective for antisense suppression than the tissue specific tomato ChiP promoter. Antisense suppression of S-RNase correlated with low sense SA2 transcript levels and high antisense SA2 transcript levels. Untransformed hybrids that contained the N. alata SA2 allele were incompatible with N. alata SA2 pollen, while transgenic plants with suppressed SA2 gene expression accepted the pollen. The utility of this hybrid plant system for studying some aspects of antisense gene suppression is discussed.

Dysfunctional uterine bleeding in adolescents.

This retrospective, multicenter analysis was conducted on all adolescents admitted to three pediatric hospitals in Montreal, Quebec, Canada, over a 10-year period (1981-1991) with a primary diagnosis of dysfunctional uterine bleeding. The purpose was to assess the frequency of underlying medical disorders and their response to medical therapy. Sixty-one patient charts were identified. Newly diagnosed hematologic abnormalities were found in two patients (one with immune thrombocytopenic purpura and one with acute promyelocytic leukemia). Furthermore, all patients who were evaluated had normal factor VIII levels, partial thromboplastin times and prothrombin times. Twenty-nine percent of the patients had a past history of a significant medical problem. The mean age at presentation was 13.8 +/- 2.1 (SD) years. More than 50% of the patients had a history of irregular bleeding. Most patients (93.4%) responded to medical management. Only five (8.2%) required dilation and curettage. The history of irregular cycles, the early presentation after menarche, the infrequency of hematologic problems but high frequency of significant medical problems led us to conclude that the etiology of dysfunctional uterine bleeding in adolescence is often related to persistent immaturity of the hypothalamic-pituitary-ovarian axis. Medical therapy is highly effective in controlling such bleeding. Dilation and curettage is rarely required.

Massive ovarian edema with androgen secretion. A pathological and endocrine study with review of the literature.

A case of massive edema of the left ovary with virilization is described. Microscopically, massive interstitial edema with luteinization of theca and stromal cells was found. A few stromal cells contained Reinke-type crystalloids--an original observation. Peripheral concentrations of testosterone, dihydrotestosterone and androstenedione were increased. Ratios of left ovarian vein to peripheral vein concentrations were increased for all these steroids as well as for estradiol and estrone, showing that the left ovary was the source of excess androgen and estrogen secretion. The patient showed impaired gonadotropin secretion in basal conditions and after an intravenous luteinizing-hormone-releasing hormone (LHRH) stimulation test. After left oophorectomy, all steroids and gonadotropin response to LHRH returned to normal, and virilization regressed. Analysis of the endocrine changes associated with this ovarian tumor brings additional arguments for a primary role of hyperandrogenism in the impairment of gonadotropin secretion, as was also observed in other hyperandrogenic disorders including polycystic ovarian syndrome.