A weight-of-evidence approach to integrate suspended sediment source information.

Sediment monitoring, tracing and modelling are widely used to identify suspended sediment sources. Although each method has inherent limitations and uncertainties, their integration provides opportunities to form collective knowledge and encourages robust management strategies. This paper presents a Weight-of-Evidence approach to integrate multiple Lines-of-Evidence for identifying suspended sediment sources. Three sources of evidence were used: i) stream flow and suspended sediment monitoring at river gauges; ii) geochemical sediment tracing at river junctions; and iii) catchment-scale suspended sediment modelling of hillslope, gully, streambank and unsealed road erosion. We applied this approach on two data-poor catchments in Australia. Some reaches were consistently identified as major sources of sediment from all Lines-of-Evidence. However, inconsistencies between the types of evidence in other areas highlighted the high uncertainty in identifying suspended sediment sources in these areas and the need for further investigation. The integration framework maximised the use of scarce information, enabled explicit consideration of uncertainties for catchment management and identified where future monitoring and research should be targeted.

Ultrasound-guided continuous transverse abdominis plane block for abdominal surgery.

INTRODUCTION: Transversus abdominis plane (TAP) block is a new regional analgesic technique for postoperative pain in abdominal surgery. Its efficacy is not clear, and thus it needs to be explored for its regular utilisation on prolonged period. The objective was to study the continuous local anaesthetic infusion effect on postoperative analgesia. Continuous use of TAP block as an analgesic technique has not been evaluated prospectively in clinical trials. This study evaluates the efficacy of ultrasound-guided TAP block in comparison with PCA fentanyl in major abdominal surgery. MATERIALS AND METHODS: There were 20 patients in the study, allocated to TAP and control groups. The parameters measured were pain scores on a numerical rating scale (NRS) of 0-10 at various time intervals and the amount of fentanyl used as rescue analgesia. Patient satisfaction scores were recorded in the TAP block group and along with any complications related to the block. RESULTS: The postoperative median pain scores on coughing on day one were 6.0 for control group and 2.0 for the TAP group (P = 0.02); on day two, the equivalent scores were 7.0 and 2.0 (P = 0.01). The fentanyl requirement at one hour was 203 µ for the control group and 78 µg for the TAP group (P = 0.03); at day one, the control and TAP requirements were 1237 µg and 664 µg respectively (P = 0.01). Three TAP patients rated their satisfaction as 'excellent', four as 'satisfied, and two as 'poor'. CONCLUSION: TAP block is a promising technique for postoperative analgesia in major abdominal surgeries. Our study demonstrated lower pain scores in the TAP group with reduced fentanyl requirement. Further, a large scale study is needed to establish the efficacy of TAP block in this setting.

Simvastatin plus nitric oxide synthase inhibition modulates remote organ damage following skeletal muscle ischemia-reperfusion injury.

UNLABELLED: Ischemia-reperfusion injury (IRI) to the lower extremities causes both local damage and serious dysfunction to remote organs, including lungs and kidneys. However, effective therapies are not available. This study aims to determine if simvastatin reduced the severity of remote damage following IRI. METHODS: Rats were given simvastatin before hind limb IRI. Lung and kidney tissues were assessed for neutrophil infiltration using myeloperoxidase assays and basement membrane damage by quantitative immunohistochemical measurement of collagen IV. The effect of nitric oxide synthase (NOS) inhibition on remote damage after IRI and simvastatin was assessed using the NOS inhibitor, L-NIO. RESULTS: Simvastatin (2 mg/kg) protected kidneys against IRI-induced neutrophil infiltration. Simvastatin also inhibited the IRI-induced activation of MMP-9 in the lungs. However, paradoxically, simvastatin exacerbated IRI-induced neutrophil infiltration into the lungs. IRI induced collagen IV degradation in the lungs but not in the kidneys. The degree of collagen breakdown in the lungs was significantly ameliorated by 2 mg/kg simvastatin. NOS inhibition markedly protected both the lungs and the kidneys against IRI-induced neutrophil infiltration but did not alter collagen IV degradation. Administration of simvastatin to L-Nio-treated animals enhanced the degree of protection against IRI-induced neutrophil infiltration in the kidneys but not in the lungs. CONCLUSIONS: Simvastatin protects against remote IRI-induced damage in the lungs and kidneys, suggesting statins may reduce the severity of IRI during major vascular surgery.

Acute effects of growth hormone on metabolism of pancreatic hormones, glucose and ketone bodies.

Controversy exists as to whether acute administration of growth hormone has insulin-like effects. In conscious dogs, acute effects on plasma flows, plasma glucose, hepatic glucose output, free fatty acids, ketone bodies, insulin, and glucagon were determined following intravenous injection of 1 mg of growth hormone extracted from the canine pituitary gland. The following results were obtained: (1) Plasma flows in the portal vein, hepatic artery and hepatic vein were significantly increased 20 min after growth hormone administration. (2) By 40 min after growth hormone, the glucose concentration in these three vessels was significantly increased. (3) Hepatic glucose output was significantly increased 60 min after growth hormone administration. (4) Free fatty acids levels were significantly but transiently increased at 20 min, while ketone body concentrations were elevated at 120-180 min. (5) The insulin levels in the three vessels demonstrated a biphasic response. In the portal vein, they were significantly higher 20 min after growth hormone and again at 150-180 min. Glucagon concentrations were increased in all three vessels by 20 min and remained elevated for the remainder of the experiment. These results do not support an acute insulin-like action of growth hormone in normal dogs.

Long-term effects of eicosapentaenoic acid on diabetic peripheral neuropathy and serum lipids in patients with type II diabetes mellitus.

The present study was undertaken to investigate the efficacy of a new, highly purified (purity greater than 91%), ethyl esterification product from natural eicosapentaenoic acid (EPA-E, C20:5 omega 3) in patients with type II diabetes mellitus (NIDDM). Hemodynamic changes were assessed at the level of the dorsalis pedis artery using an ultrasonic color Doppler duplex system before and after oral administration of EPA-E at a dose of 1800 mg/day for 48 weeks. The cross-sectional area of the dorsalis pedis artery increased significantly from 2.5 +/- 0.2 to 3.9 +/- 0.4 mm2 (48 weeks, mean +/- SE, p < 0.05). Moreover, EPA-E improved the clinical symptom (coldness, numbness) as well as the vibration perception threshold sense of the lower extremities [from 32.1 +/- 8.5 to 16.1 +/- 4.8 (48 weeks) microns]. A significant decrease of serum triglycerides was also noted by EPA-E administration. Furthermore, significant decrease of the excretion of albumin in urine [from 24.4 +/- 3.3 to 13.9 +/- 1.8 (48 weeks) mg/g.Cr, p < 0.05]. The results of this study suggest that EPA-E has significant beneficial effects on diabetic neuropathy and serum lipids as well as other diabetic complications such as nephropathy and macroangiopathy.

Counterproductive effects of sodium bicarbonate in diabetic ketoacidosis.

Although a growing body of evidence supports that alkali therapy in diabetic ketoacidosis (DKA) might be counterproductive, our knowledge about the consequences of this treatment on ketone metabolism is limited. Consequently, we performed clinical and animal studies to further examine this topic. The clinical studies assessed seven patients with DKA treated with continuous insulin infusion at a low dosage. Three of them also received sodium bicarbonate (NaHCO3), whereas the remaining four acted as controls. The group receiving NaHCO3 showed a 6-h delay in the improvement of ketosis as compared with controls. In addition, there was an increase in acetoacetate (AcAc) levels during alkali administration, followed by an increase in 3-hydroxybutyrate (3-OHB) level after its completion. Significant differences were not found between groups in the response of plasma glucose to the overall therapy. The animal study examined the effects of a NaHCO3-rich perfusate on the hepatic production of ketones with the in situ rat-liver preparation. Alkali loading resulted in an immediate increase in the AcAc level followed by increases in both the 3-OHB level and the 3-OHB/AcAc ratio after its completion. Hepatic ketogenesis increased even further, to about twice the basal level, after termination of the NaHCO3 loading. This investigation confirms that alkali administration augments ketone production and unravels an effect of bicarbonate infusion that promotes a selective build up of AcAc in body fluids. The data support that alkali therapy in DKA has nonsaltuary effects in the metabolism and plasma levels of ketones.

Effect of growth hormone on hepatic glucose and insulin metabolism after oral glucose in conscious dogs.

This study examined the effect of growth hormone (GH) on hepatic glucose metabolism and on the fractional extraction of insulin and glucagon after oral glucose administration. GH treatment [canine GH (0.75 mg/day for 7 days)] significantly increased basal portal vein and hepatic artery flow (P < 0.01 compared with pre-GH treatment). After GH treatment and after oral glucose, glucose levels significantly exceeded those before GH at 100 and 120 min in arterial and portal vein plasma and 120 min in the hepatic vein. The net hepatic uptake of glucose was similar before and after GH treatment. The increment of net nonhepatic splanchnic insulin balance above basal was 131 +/- 31 mU.kg-1.3 h-1 before and 272 +/- 46 mU.kg-1.3 h-1 after GH treatment (P < 0.05). An increase in fractional hepatic extraction of insulin occurred before GH treatment and was significantly greater at 60 min. In summary, despite the increased insulin content after GH administration, there was no change in hepatic uptake of glucose, indicating that the liver was also the site of insulin resistance.

Thyroid hormone inhibition of intermediary metabolism in dog thyroid slices stimulated by different agonists.

The role of thyroid hormones in a short loop feedback in the thyroid is controversial. This process was studied in dog thyroid slices stimulated by TSH, carbachol and phorbol esters. Incubation of thyroid slices with T3 and T4 for 1 hour inhibited the subsequent stimulation of glucose oxidation induced by carbachol and phorbol esters but not by TSH. T3 also inhibited the stimulation of 32P incorporation into phospholipids stimulated by these two agonists. Glucose oxidation stimulated by TSH, carbachol and 12-0-tetradecanoyl-phorbol-13-acetate (TPA) was inhibited by rT3 and the inhibition was not reversed by methimazole, which did abolish the inhibition induced by iodide, MIT and DIT. TSH stimulation of cAMP was not blocked by T3 or T4 but was by rT3 and MIT- and DIT. The mechanism of such inhibition appears to be complex, possibly involving formation of iodide from rT3, MIT and DIT but also dependent on the intact iodothyronine. Moreover, our data suggest that T3 and T4 exert their inhibition on the thyroid through the phospholipids cascade and this mechanism is probably independent on the release of iodide from these iodocompounds.

Oral insulin in diabetic dogs.

Bovine crystalline insulin, mixed with an absorption enhancer, was loaded by hand into gelatin capsules, which were then coated with an azopolymer designed to deliver the insulin in the upper colon. In 34 experiments with 14 pancreatectomized mongrel dogs of both sexes, the coated capsules were administered orally after a pre-dose period of 1 h. The dogs had cannulae in the portal vein, hepatic vein and femoral artery and Doppler flow probes on the portal vein and hepatic artery. Insulin and food were withdrawn the day before an experiment. Responses measured were plasma glucose, plasma insulin, hepatic glucose production rate, hepatic plasma flow rate and plasma glucagon-like immunoactivity (GLI). Control experiments, with capsules without insulin, produced small changes from 'pre-dose' values. Insulin-containing capsules, without the azopolymer coating, resulted in some early changes consistent with upper gastrointestinal absorption. Single oral doses (66 to 400 nmol/kg) of insulin in completely coated capsules produced peaks of portal plasma insulin and transient decreases in plasma glucose, hepatic glucose production, hepatic plasma flow and plasma GLI. The changes usually began 1.5-2 h after administration of a single dose, and lasted for up to 3 h, but were not significantly related to the dose of insulin. Multiple oral doses of insulin, given at 1.5-h intervals, resulted in multiple peaks of plasma insulin, a continuing dose-dependent fall in plasma glucose to near-euglycaemia with the highest dose, and profound decreases in hepatic glucose production and plasma GLI. These data demonstrate that insulin absorbed from the gastrointestinal tract causes changes in glucose metabolism in the diabetic dog that are consistent with the action of insulin primarily on the liver and that repeated oral doses are necessary to correct the hyperglycaemia.

Effect of oral glucose ingestion on hepatic non-esterified fatty acids and ketone body metabolism in normal dogs.

The time course of changes in hepatic lipid metabolism (non-esterified fatty acids (NEFA), ketone body) after ingestion of glucose was assessed in normal dogs. Glucose ingestion suppressed significantly (p less than 0.01) the amount of NEFA reaching the liver (12.4 +/- 1.0 to a nadir of 2.9 +/- 0.6 mumol/kg/min at 80 min) and increased significantly (p less than 0.05) net hepatic balance (-1.8 +/- 0.6 to 0.5 +/- 0.4 mumol/kg/min at 120 min). After glucose ingestion, the amount of total ketone body presented to the liver decreased significantly (p less than 0.05) to a nadir of 1.1 +/- 0.4 mumol/kg/min at 60 min and gradually increased after 120 min. These changes reflect the increased insulin secretion induced by glucose ingestion. The hyperinsulinemia would inhibit peripheral lipolysis and stimulate esterification of fatty acids. It would reduce ketone body concentration both by a direct effect on hepatic production as well as the consequence of diminished NEFA levels. In summary, the present study clearly demonstrated the time course changes in NEFA and ketone body level after oral glucose ingestion.

Beta-adrenergic stimulation contributes to incretin effect in conscious dogs.

Oral glucose administration increases insulin secretion to a greater extent than peripheral glucose infusion (incretin effect). It also augments protal vein blood flow, hepatic uptake of glucose, and fractional hepatic extraction of insulin. The mechanisms for these various effects are not known but could involve both neurogenic stimuli and gut hormones. The present studies examined the effect of a non-nutrient drink, 1 g/kg body wt oral mannitol, on these parameters during an intravenous glucose infusion in conscious dogs. The dogs had chronically implanted Doppler flow probes on the portal vein and hepatic artery and catheters in the portal vein, hepatic vein, and femoral artery. After a 30-min control period, an infusion of atropine, propranolol, phentolamine, or propranolol and phentolamine was begun. Thirty minutes later, glucose (13 mg.kg-1.min-1) was then infused into a peripheral vein for 120 min with continuation of the atropine and adrenergic blockade. Water or mannitol (10% solution) was administered orally 50 min after the initiation of the glucose infusion. Mannitol, but not water, significantly enhanced the insulin response to intravenous glucose, as indicated by higher insulin concentrations in the portal vein as well as more rapid reduction of the plasma glucose. This incretin effect was significantly attenuated by infusion of propranolol but not by atropine or phentolamine. Mannitol did not increase portal vein blood flow or have any effect on the hepatic uptake of glucose or the fractional hepatic extraction of insulin. Thus absorption of nutrient is not necessary for the incretin effect but is for the increased portal vein blood flow and increased fractional extraction of insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathway and carbon sources for hepatic glycogen repletion in dogs.

The present studies were undertaken to quantitate the relative contributions of the indirect and direct pathways for hepatic glycogen repletion and to determine the role of splanchnic tissues in provision of C precursors used for the indirect pathway. For this purpose, we administered oral glucose (1.4 g/kg) enriched with [1-14C]glucose to 18-h fasted dogs and measured net hepatic and net gastrointestinal glucose, lactate, and alanine balance, hepatic and gastrointestinal fractional extraction [( 3H]lactate), release and uptake of lactate, as well as the total amount of hepatic glycogen formed from the oral glucose and the 14C labeling pattern of the glycogen-glucose C. Although net hepatic glucose uptake (8.7 +/- 0.6 g, 27% of the oral load) exceeded the amount of glycogen formed from the oral glucose (6.3 +/- 1.1 g), analysis of radioactivity in C-1 of the glycogen glucose indicated that nearly 50% of the glycogen was formed by the indirect pathway. Net hepatic uptake of lactate (1.4 +/- 0.1 g) and alanine (1.5 +/- 0.1 g) could account for greater than 90% of glycogen formed by the indirect pathway if all of the lactate and alanine taken up by the liver had been incorporated into glycogen. Release of lactate and alanine by splanchnic tissues approximated the amount of lactate and alanine taken up by the liver. However, in addition to taking up lactate, the liver also produced nearly as much lactate as the gastrointestinal tract (1.8 +/- 0.2 vs. 2.0 +/- 0.3 g, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of intermediary metabolism by amiodarone in dog thyroid slices.

Amiodarone, an iodine-containing antiarrhythmic drug, has been reported to interfere with thyroid function and thyroid hormone metabolism. We studied the effects of amiodarone on basal and agonist [thyroid-stimulating hormone (TSH), phorbol ester, or carbachol]-stimulated glucose oxidation, 32PO4 incorporation into phospholipids, and adenosine 3',5'-cyclic monophosphate (cAMP) concentration in dog thyroid slices. Slices were preincubated with amiodarone at 37 degrees C for 1 h before the addition of agonist and the appropriate radioisotope. cAMP stimulation was measured after 20 min, glucose oxidation for 45 min, and 32PO4 incorporation into phospholipids for 2 h. Amiodarone (0.5 mM) had no effect on basal 14CO2 formation or 32PO4 incorporation into phospholipids but significantly inhibited TSH, phorbol ester, and carbachol stimulation of these parameters. It also inhibited cAMP stimulation by TSH. Inhibition of TSH-stimulated [14C]glucose oxidation was also obtained with another iodide-containing compound, iopanoic acid (0.5 mM), but not with iothalamate (up to 10 mM). Inhibition by amiodarone was still present, but to a lesser extent, when it was added at the same time as the agonist. Inhibition of stimulated [14C]glucose oxidation persisted even after the slices were incubated without amiodarone for 6 h. Inhibition by amiodarone, in contrast to that by inorganic iodide, was not prevented by 1 mM methimazole added at the same time as amiodarone. These results indicate that the inhibitory effects of amiodarone on thyroid function are not due to dissociation of iodide from the molecule.

Phosphoinositides metabolism in primary culture of dog thyroid cells: effects of thyrotropin and carbachol.

Thyrotropin (TSH) and carbachol stimulated in a dose-dependent manner the accumulation of 3H-glycerophosphoinositol (GPI), 3H-inositol monophosphate (IP1), 3H-inositol bisphosphate (IP2) and 3H-inositol trisphosphate (IP3) in primary cultures of dog thyroid cells prelabeled with myo-[2-3H]inositol. TSH, 250 mU/mL, stimulated 3H-IP3 level after a 10-minute incubation while 10 mU/mL TSH increased it during a 60-minute incubation. The effect of carbachol was more rapid and greater than that of TSH. Carbachol, 100 mumol/L, elevated 3H-IP3 after a 2-minute incubation and 3H-IP3 formation was increased by as little as 1 mumol/L carbachol. TSH stimulation was observed only if the cells were deprived of TSH for 5 days before being labeled with 3H-inositol. Prolongation of the labeling period or addition of TSH, (Bu)2cAMP or carbachol during the labeling increased 3H-inositol incorporation into polyphoinositides (PIPs). When the cells were labeled without any other addition, control and TSH-stimulated 3H-IP3 levels increased in parallel with 3H-PIP levels. However, TSH or carbachol-stimulated 3H-IP3 levels did not increase in proportion to 3H-PIPs level when the cells were labeled with TSH or (Bu)2cAMP. Thus, the ratio of 3H-IP3/3H-PIPs (both control and TSH or carbachol-stimulated) decreased in the cells labeled with TSH or (Bu)2cAMP, which might reflect TSH stimulation of 3H-inositol incorporation into PIPs pool(s) that do not participate in hormone-induced hydrolysis of PIPs.(ABSTRACT TRUNCATED AT 250 WORDS)

Unilateral gynecomastia associated with thoracotomy following resection of carcinoma of the lung.

A 66-year-old man developed right painful gynecomastia following resection of a well-differentiated squamous cell carcinoma from the right upper lobe. In 1979, he had a well-differentiated squamous cell carcinoma resected from the left lower lobe. Extensive investigation did not reveal any definite indication of metastases or residual carcinoma. There was no evidence for thyroid, liver, or renal disease. His plasma testosterone was 400 ng/dl, estradiol was 43 pg/ml, LH 3.5 ng/ml, FSH 13.1 mIU/ml and HCG less than 5 mIU/ml. Since no other cause of gynecomastia was apparent , it was attributed to the right thoracotomy.

Effects of lithium on stimulated metabolic parameters in dog thyroid slices.

Thyroid abnormalities may develop during chronic lithium therapy for affective disorders. Lithium, like iodide, inhibits TSH stimulation of adenylate cyclase and thyroid hormone release. The present study examined the effect of lithium on stimulation of intrathyroidal intermediary metabolism by several agonists. LiCl (5 mmol/l) did not inhibit basal cAMP, glucose oxidation or 32P incorporation into phospholipids in dog thyroid slices. Although LiCl inhibited TSH stimulation of cAMP, it did not abolish the hormone's effect on cAMP-dependent protein kinase. The stimulation of iodide organification, glucose oxidation or 32P incorporation into phospholipids by TSH, carbachol and phorbol esters was not inhibited by lithium. This is in contrast to the effects of iodide, which inhibited stimulation of glucose oxidation and 32P incorporation into phospholipids by various agonists. Thus, although both lithium and iodide inhibited TSH-stimulated cAMP formation, they act differently on intrathyroidal intermediary metabolism.

Intracellular Ca2+ mobilization by thyrotropin, carbachol, and adenosine triphosphate in dog thyroid cells.

The effect of TSH, carbachol (CC), and ATP on intracellular calcium concentration ([Ca2+]i) in primary cultures of dog thyroid cells was examined using the fluorescent Ca2+ indicator fura-2. TSH caused an increase in [Ca2+]i at 37 C, but not 22 C, while it increased cAMP formation in these cells at both 22 and 37 C. CC and ATP increased [Ca2+]i at both 22 and 37 C. The CC-induced increase in [Ca2+]i was under muscarinic receptor control, and it was biphasic, with an initial spike followed by a sustained increase at a lower level. TSH and ATP were weaker agonists compared to CC, since maximal doses of TSH (100-500 mU/ml) and ATP (100-500 microM) increased [Ca2+]i by 40-70% over basal levels, compared to a 2- to 4-fold increase in [Ca2+] induced by maximal doses of CC (10-50 microM). The TSH-induced increase in [Ca2+]i was transient, returning to basal levels within 1-2 min after application of the agonist. All three agents were able to transiently increase [Ca2+]i to be internal stores. In the presence of the inorganic Ca2+ channel blockers La3+, Ni2+, and Co2+, the peak [Ca2+]i change was little affected, while the persistent response to CC and ATP was blocked, indicating dependence of this phase on influx of Ca2+. Paradoxically, these channel blockers abolished the effect of TSH on [Ca2+]i. TSH stimulation of cAMP formation was also inhibited 80-90% by these blockers, but not in Ca2+-free/EGTA buffer. These results suggest that the Ca2+ channel blockers may have actions in addition to inhibition of Ca2+ entry in these cells. TMB-8 [8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate HCl] specifically blocked both the initial and sustained increase induced by CC, while having no effect on ATP or TSH-induced [Ca2+]i, suggesting that TMB-8 may not be a general antagonist of Ca2+ mobilization. Activators of protein kinase-C, such as phorbol esters or an analog of diacylglycerol, inhibited the [Ca2+]i rise induced by all the three agonists used, indicating a regulatory role of protein kinase-C activation on [Ca2+]i in these cells. In FRTL-5 cells, [Ca2+]i was also increased by TSH and ATP, but not by CC. ATP, however, was a more effective agonist than in dog thyroid cells, while TSH increased [Ca2+]i by a similar magnitude in both cell types. The results of the present study demonstrate that TSH, albeit of lesser potency than CC, increases [Ca2+]i by causing intracellular Ca2+ mobilization in cultured dog thyroid cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of iodide on glucose oxidation and 32P incorporation into phospholipids stimulated by different agents in dog thyroid slices.

Since iodide (I-) inhibits TSH stimulation of cAMP formation, which mediates most of the effects of the hormone, it has been assumed that this accounts for the inhibitory action of iodide on the thyroid. However, TSH stimulation of 32P incorporation into phospholipids and stimulation of thyroid metabolism by other agonists, such as carbachol, phorbol esters, and ionophore A23187, is not cAMP mediated. The present studies examined the effect of iodide on stimulation of glucose oxidation and 32P incorporation into phospholipids by TSH and other agonists to determine if the inhibition of cAMP formation was responsible for the action of iodide. Preincubation of dog thyroid slices for 1 h with iodide (10(-4) M) inhibited TSH-, (Bu)2cAMP-, carbachol-, methylene blue-, 12-O-tetradecanoyl phorbol-13-acetate-, ionophore A23187-, prostaglandin E1-, and cholera toxin-stimulated glucose oxidation. I- also inhibited the stimulation by TSH, 12-O-tetradecanoyl phorbol-13-acetate, carbachol, and ionophore A23187 of 32P incorporation into phospholipids. The inhibition was similar whether iodide was added 2 h before or simultaneously with the agonist. I- itself sometimes stimulated basal glucose oxidation, but had no effect on basal 32P incorporation into phospholipids. The effects of iodide on basal and agonist-stimulated thyroid metabolism were blocked by methimazole (10(-3) M). When dog thyroid slices were preloaded with 32PO4 or [1-14C]glucose, the iodide inhibition of agonist stimulation disappeared, suggesting that the effect of iodide involves the transport process. In conclusion, I- inhibited stimulation of glucose oxidation and 32P incorporation into phospholipids by all agonists, indicating that the effect is independent of the cAMP system and that iodide autoregulation does not only involve this system. Oxidation and organification of iodide are necessary for the inhibition. The ability of iodide to decrease glucose and 32PO4 transport may play an important role in thyroid autoregulation.

Exercise and deficient carbohydrate storage and intake as causes of hypoglycemia.

Exercise is associated with a marked increase in glucose uptake by muscle, which is initially supported by breakdown of hepatic glycogen and subsequently by increased gluconeogenesis. If hepatic glucose production is inadequate, hypoglycemia results. During exercise there is decreased plasma insulin and increased catecholamines, glucagon, cortisol, and growth hormone, which contribute to but are not essential for the increased hepatic output of glucose. Although insulin concentrations fall, insulin sensitivity is increased. However, the augmented glucose uptake by muscle is due to other factors. The symptoms of exhaustion during exercise are not due to hypoglycemia, and prevention of hypoglycemia may not prolong the time of exercise to exhaustion. During severe caloric restriction, hepatic glucose production decreases and free fatty acids and ketone bodies become important sources of calories. Although under these circumstances hepatic gluconeogenesis is usually sufficient to prevent hypoglycemia, with very severe caloric restriction hypoglycemia can result. With starvation, insulin concentrations fall while growth hormone and glucagon increase. Frequently the usual symptoms of hypoglycemia are absent in individuals with hypoglycemia from severe caloric restriction. Hypoglycemia from severe caloric restriction has not been totally restricted to underdeveloped areas of the world. In such patients no endocrine abnormalities have been found, and hypoglycemia has persisted despite administration of large amounts of carbohydrate. Pregnancy and lactation could predispose to hypoglycemia in the face of inadequate caloric intake.