Regulation of breathing in hyperthyroidism: relationship to hormonal and metabolic changes

We sought to examine the breathing pattern, inspiratory drive and chemosensitivity of hyperthyroid patients and to explore the interactions between their thyroid hormones, basal metabolism and chemosensitivity. We studied 15 hyperthyroid patients and 15 sex- and age-matched controls. Thyroid hormone levels, arterial blood gas tensions, lung volumes, diffusing capacity for CO, maximal respiratory pressures and oxygen uptake measurements were performed. Breathing pattern and mouth occlusion pressure (P0.1), as well as ventilatory and P0.1 responses to hyperoxic progressive hypercapnia and isocapnic progressive hypoxia, were also evaluated. Compared with the control subjects, the hyperthyroid patients showed significantly lower resting arterial CO2 tension, tidal volume and significantly higher mean inspiratory flow and P0.1. Ventilatory and P0.1 responses to CO2 and hypoxia were also greater in the hyperthyroid patients than in the control group. All these changes returned to normal after treatment. In the patients, significant relationships between tri-iodothyronine and P0.1, P0.1 response to hypoxia, and P0.1 response to hypercapnia were found. In contrast, in hyperthyroidism there was no relationship between oxygen uptake and P0.1 response to hypoxia. We conclude that hyperthyroid patients exhibit a significant relationship between their thyroid hormone levels and their increased inspiratory drive and chemosensitivity.     

Metabolic and hormonal mechanisms of mineral metabolic adaptation to induced hypokinetics in rats

During simulated hypokinetics, many biological functions have a tendency to stabilize at different levels with the passing of time. In this experiment, hypokinetic exposure was induced in albino rats by the suspension method for 5 weeks. A new plateau in urinary K+ excretion was attained during the third week, after a transient decrease during the first week. Since the formation of this steady plateau is considered a manifestation of the adaptation of this function, the hypokinetic exposure period was divided into a prestabilized phase and a stabilized phase. To ascertain the biochemical mechanisms of this adaptation process, the effects of aldosterone and anti-aldosterone substances (e.g., tetracycline) on K+ and Na+ excretion patterns in each phase were investigated. Decreasing aldosterone activity in the prestabilized phase and increasing activity in the stabilized phase are recognized as one of the main factors in the renal adaptation process to hypokinetics.     

Effect of somatostatin immunoneutralization on gastric acid and pancreatic enzyme secretion in anesthetized rats

The involvement of somatostatin in urethane-anesthesia-evoked suppression of gastric acid secretion has been described. The present study has examined the role of endogenous somatostatin in diminished pancreatic enzyme secretion during anesthesia, while monitoring acid secretion concurrently. Rats were anesthetized with either urethane or sodium pentobarbital. An indwelling catheter was placed into the right jugular vein. The esophagus and the pylorus were ligated, and the stomach was perfused with saline. The common bile duct was ligated at the hepatic hilum, and cannulated at the duodenal end of the duct for collecting pure pancreatic juice. Purified somatostatin monoclonal antibody (CURE.S6) or control antibody (keyhole limpet hemacyanin, KLH) was injected iv in increasing doses (0.05; 0.15; 0.5; and 1.5 mg) every 30 min (n = 6). Gastric acid and pancreatic amylase secretions were measured. The effect of the antibodies on CCK-8-stimulated (0.25-2.50 nmol/kg/h) pancreatic amylase secretion was also tested. During urethane anesthesia somatostatin antibody induced a dose-dependent increase in acid output, while control antibody did not change it. Basal pancreatic amylase secretion was not affected by either somatostatin or by control antibody. Pancreatic secretory responses to high but not to low doses CCK-8 were found to be significantly increased following immunoneutralization of somatostatin. In sodium pentobarbital-anesthetized rats somatostatin antibody stimulated basal acid secretion but did not affect basal pancreatic amylase secretion. Our data indicate that in anesthetized rats endogenous somatostatin mediates suppression of basal gastric acid secretion but not that of basal pancreatic amylase secretion, and this action does not depend on the type of anesthesia. Furthermore, endogenous somatostatin may play a physiological role in modulating stimulated pancreatic enzyme secretion in this species.     

Effect of anesthetic methods on hemodynamics and metabolic changes caused by hepatic ischemia and reperfusion in pigs

The effects of halothane, isoflurane and epidural anesthesia combined with isoflurane on hemodynamic and metabolic changes caused by hepatic ischemia and reperfusion were studied in 16 pigs. Hepatic arterial and portal venous blood flows were measured electromagnetically. Lactate pyruvate ratio (L/P) and arterial ketone body ratio (AKBR) were calculated as markers of hepatic aerobic metabolism. Total hepatic blood flow (THBF), cardiac output (CO) and THBF/CO showed no significant differences among three anesthetic methods in ischemic and reperfusion period. In the group with epidural anesthesia combined with isoflurane, L/P was significantly lower and AKBR was significantly higher compared with the data obtained in ischemic period. However, hepatic metabolism was severely disturbed after the reperfusion of the liver in all three groups. Especially, halothane group showed the most remarkable decrease in AKBR. In summary, epidural anesthesia will be useful for aerobic hepatic metabolism because of inhibition of the release of endogenous cathecolamines, but hepatic metabolism will not be maintained following hepatic ischemia and reperfusion.     

Effect of nicotinic acid on cholera-induced fluid movement and unidirectional sodium fluxes in rabbit jejunum

Cholera toxin produces intestinal secretion and elevation of intestinal cyclic AMP. Nicotinic acid has been shown to prevent these responses. The effect of nicotinic acid on cholera toxin-induced secretion could be caused by decreased plasma-to-lumen flux, increased lumen-to-plasma flux, or a combination of both. The purpose of this study was to define the effects of nicotinic acid on net fluid movement and unidirectional sodium fluxes in rabbit jejunal loops exposed to cholera toxin. In the untreated animals receiving no nicotinic acid, the cholera toxin-exposed loops secreted 0.91 ml/cm/4h above the control loops receiving no cholera toxin (p < 0.01). On the other hand, pretreatment with 100 mg/kg nicotinic acid caused a striking decrease in secretion in the cholera toxin loop, so that the cholera toxin loop was not significantly different from the control loop. Unidirectional sodium fluxes in untreated animals showed that cholera toxin caused an increase in the plasma-to-lumen flux and a decrease in the lumen-to-plasma flux. Both effects were abolished by pretreating the animals with nicotinic acid. These studies indicate that nicotinic acid prevents cholera toxin-induced secretion by restoring the unidirectional fluxes to control levels.     

Effect of camel urine on the cytological and biochemical changes induced by cyclophosphamide in mice

The purpose of this study was to investigate whether mandatory universal precautions changed nurses' body fluid exposure and reporting rates, hepatitis B vaccination rates, and human immunodeficiency virus (HIV) testing rates. Random cross-sectional surveys of nurses in Tennessee were conducted in 1991 and 1993 (n = 145 in 1991; n = 143 in 1993). The questionnaire in both surveys included frequency of body fluid exposures and reporting in the past year, and whether or not the respondent had received the hepatitis B vaccine or had been HIV tested. Findings indicated that self reported needlestick injuries decreased by 69%, and other sharps injuries decreased by 81%. Only 4.1% of all exposure incidents reported on this anonymous survey were reported to employee health officials, as required. Body fluid exposure incidents were the most common form of exposure (81%) and the most underreported. Hepatitis B vaccinations significantly increased (61.4% to 82.5%), with a nonsignificant increased in HIV testing (47.2% to 55.6%) from 1991 to 1993. Findings of this study suggest that the universal precautions regulatory mandate has been effective in increasing nurses' compliance to universal precautions. Body fluid contacts were significantly underreported and showed no decrease between 1991 and 1993.     

Effect of glutamine supplementation on changes in the immune system induced by repeated exercise

The ability of lymphocytes to proliferate and generate lymphokine activated killer (LAK) cell activity in vitro is dependent on glutamine. In relation to intense exercise the lymphocyte concentration, the proliferative response, the natural killer and LAK cell activity, and the plasma glutamine concentration decline. It has been hypothesized that in relation to physical activity a lack of glutamine may temporarily affect the function of the immune system. PURPOSE: The purpose of this study was to examine the influence of glutamine supplementation on exercise-induced immune changes. METHODS: In a randomized cross-over placebo-controlled study, eight healthy male subjects performed three bouts of ergometer bicycle exercise lasting 60, 45, and 30 min at 75% of their VO2max separated by 2 h of rest. RESULTS: The arterial plasma glutamine concentration declined from 508 +/- 35 (pre-exercise) to 402 +/- 38 microM (2 h after the last exercise bout) in the placebo trial and was maintained above pre-exercise levels in the glutamine supplementation trial. The numbers of circulating lymphocytes and the phytohemagglutinin-stimulated lymphocyte proliferative response declined 2 h after, respectively, during each bout of exercise, whereas the LAK cell activity declined 2 h after the third bout. Glutamine supplementation in vivo, given in the described doses at the specific times, did not influence these changes. CONCLUSION: The present study does not appear to support the hypothesis that those aspects of postexercise immune changes studied are caused by decreased plasma glutamine concentrations.     

Effect of quercetin on chemiluminescence of human platelets induced by arachidonic acid

Arachidonic acid (AA)-induced platelet chemiluminescence (CL) was measured with a lumiphotometer. Quercetin remarkably inhibited the CL, the IC50 of quercetin was 3 mumol.L-1. When quercetin plus aspirin, which inhibits only cyclooxygenase, was added, the inhibitory rate of platelet-CL obviously increased (P < 0.01). On the other hand, the quercetin had a scavenging effect on superoxide anion radical using alkaline sodium dithionite solution generation. The IC50 was 20.9 mumol.L-1. In addition, superoxide dismutase of 0.1 mg.ml-1 inhibited the platelet-CL by 97.8%, while mannitol, a hydroxyl radical scavenger, only by 43.3% at a concentration of 80 mg.ml-1. These results suggest that the mechanism of the inhibiting AA-induced platelet-CL by quercetin was associated with scavenging the superoxide anion radical directly and with inhibiting the cyclooxygenase.     

Glucose-induced changes in renal haemodynamics in proteinuric type 1 (insulin-dependent) diabetic patients: inhibition by acetylsalicilic acid infusion

The effect of hyperglycaemia on renal function in diabetic nephropathy remains poorly understood. We investigated the renal haemodynamic response to an acute plasma glucose rise from sustained euglycaemia to sustained hyperglycaemia in eight persistently proteinuric Type 1 (insulin-dependent) diabetic patients. Studies were performed in a double-blind cross-over manner after i.v. injection of 450 mg lysine acetylsalicilate (equivalent to 250 mg acetylsalicilic acid) or equal volume of 0.9% NaCl (isotonic saline). In the isotonic saline experiments hyperglycaemia produced a significant rise, by approximately 35%, in glomerular filtration rate in all patients from 41.5 +/- 5.2 to 55 +/- 6 ml.min-1.1.73 m-2 (p < 0.005) and an increase in sodium paraminohippurate clearance from 178 +/- 22.7 to 220 +/- 20.0 ml.min-1.1.73 m-2 (p < 0.05). These changes took place within the first 30 min of glucose infusion and were maintained for a 90 min hyperglycaemic period. Filtration fraction did not change significantly. Infusion of lysine acetylsalicilate lowered baseline glomerular filtration rate (isotonic saline vs lysine acetylsalicilate 41.5 +/- 5.2 vs 30.0 +/- 5.7 ml.min-1.1.73 m-2; p < 0.05) and significantly blunted the rise in glomerular filtration rate during hyperglycaemia (glomerular filtration rate increment: saline vs lysine acetylsalicilate: 13.6 +/- 2.8 vs 5.3 +/- 1.8 ml.min-1.1.73 m-2; p < 0.005). The effects on renal plasma flow were similarly blunted. In five additional patients, time- and volume-controlled isotonic saline experiments during sustained euglycaemia showed no significant changes in glomerular filtration rate and sodium paraminohippurate clearance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Energy and water metabolism, body composition, and hormonal changes induced by 42 days of enforced inactivity and simulated weightlessness

Inactivity causes profound deleterious changes. We investigated in eight healthy men the impact of a 42-day head-down bed rest (HDBR) on energy and water metabolism and their interrelationships with body composition (BC) and catabolic and anabolic hormones. Total energy expenditure (TEE), total body water, water turnover, and metabolic water formation were assessed by the doubly labeled water method 15 days before and for the last 15 days of HDBR. Resting energy expenditure was determined by indirect calorimetry, and BC was determined by dual energy x-ray absorptiometry. Urinary excretion of cortisol, GH, normetanephrine, metanephrine, urea, and creatinine were measured daily. HDBR resulted in significant reductions in body weight (2%), total body water (5%), metabolic water (17%), and lean body mass (LBM; 4%), but fat mass and water turnover did not change. Segmental BC showed a decreased LBM in legs and trunk, whereas fat mass increased, no significant changes were noted in the arms. The hydration of LBM was unchanged. TEE and energy intake decreased significantly (20% and 13%), whereas resting energy expenditure was maintained. Expenditure for physical activity dropped by 39%. Subjects were in energy balance during HDBR, whereas it was negative during the control period (-1.5 MJ/day). There were decreases in urinary normetanephrine (23%) and metanephrine (23%), but urinary cortisol (28%; weeks 2 and 3), GH (75%; weeks 2-4), and urea (15%; weeks 3 and 4) increased. It was concluded that during prolonged HDBR no relevant modifications in water metabolism were triggered. BC changes occurred in the nonexercised body segments, and the reduction in TEE was due to inactivity, not to LBM loss. Moreover, body weight alone does not accurately reflect the subject's energy state, and energy balance alone could not explain the body weight loss, which involves a transient metabolic stress.     

Acute and delayed hormonal changes in mitral stenosis treated by balloon valvulotomy

The role of left atrial and aortic pressures on the secretion of the main hormones controlling blood volume is still subject to debate in humans. Because of increased mean left atrial pressure and decreased mean aortic pressure produced by balloon inflation in patients with mitral stenosis treated with balloon valvulotomy, the hormonal changes occurring acutely (group II of patients) were measured. The same studies (group I patients) were also performed 48 hours after this treatment, a period at which left atrial pressure permanently diminished. Inflation of the balloon resulted in a decrease in plasma renin activity and increases in plasma atrial natriuretic factor (ANF) and plasma arginine vasopressin (AVP). Forty-eight hours after balloon valvulotomy, which had produced a decrease in left atrial pressure, plasma ANF was lower (58.9 +/- 7.9 vs 95.3 +/- 11.9 pg/ml; p < 0.001), and plasma renin activity (2,575 +/- 533 vs 960 +/- 113 pg/ml/hour; p < 0.01), plasma angiotensin II (25.0 +/- 4.1 vs 9.3 +/- 1.3 pg/ml; p < 0.001) and plasma aldosterone (181.7 +/- 36.7 vs 139.9 +/- 19.8 pg/ml; p < 0.05) were higher than their respective control levels 24 hours before treatment of the stenosis. In contrast, plasma AVP (3.7 +/- 0.25 vs 4.4 +/- 0.31 pg/ml; p = 0.001) diminished moderately along with plasma osmolality (282.4 +/- 0.1 vs 286.2 +/- 0.6 mOsm/kg; p < 0.001). Urinary sodium excretion was also examined before and after balloon valvulotomy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular and hormonal responses to cold pressor test in insulin-dependent diabetic adolescents with microalbuminuria

The effect of cyanide (10(-7) M), thiocyanate (10(-4) M) and nicotine (10(-7) M) on the concentration-response curves of 5-hydroxytryptamine, norepinephrine and epinephrine were investigated in human isolated umbilical arteries and veins. Cyanide significantly affected the responses of arterial strips to 5-hydroxytryptamine, norepinephrine and epinephrine: It caused significant leftward shifts of the 5-hydroxytryptamine concentration-response curves and significantly potentiated the contractile effects of norepinephrine and epinephrine in the case of norepinephrine, and epinephrine concentration reached 10(-6) and 10(-7) M respectively in the bath medium. Cyanide did not show any significant effect on the concentration-response curves of 5-hydroxytryptamine, norepinephrine and epinephrine in veins. Nicotine interacted with the response of adrenergic agonists both in arteries and veins; in arteries it potentiates the contractile response of epinephrine; in veins, it inhibited the dilatory responses of norepinephrine and potentiated the contractile effect of high concentration of epinephrine (10(-6) M). Thiocyanate did not cause any difference on any cumulative concentration-response curves either on the vessels. However, none of these individual effects of cyanide and nicotine were observed when the cyanide, thiocyanate and nicotine were added in combination in the isolated organ bath medium.     

Mammographic changes in postmenopausal women on hormonal replacement therapy

The purpose of this study was to investigate the extent of the effects of hormonal replacement therapy (HRT) on the mammographic breast pattern in postmenopausal women. In a hospital-based study mammographic examinations of 81 postmenopausal women were evaluated retrospectively, before and after 1-2 years of treatment with oestrogens or a combination of oestrogens and progestagens. Each individual mammographic film was examined separately, and the glandular tissue was classified according to a modified Wolfe classification. In a screening-centre-based study two consecutive mammograms, with a 2-year interval, of 645 women, of whom 70 were using some kind of hormone therapy, were evaluated retrospectively. In the hospital-based study 31 % of patients treated with combination HRT showed an increase in fibroglandular tissue compared with only 8.7 % in the group treated with oestrogens alone. The difference was statistically significant (p = 0.046). In the screening-based study 14.3 % of the women using hormonal therapy showed an increase, whereas in the non-users no increase was found (p = 1.24 x 10(-10)). After beginning HRT many women (between 14 and 25 % in our experience) can be expected to undergo a mammographically detectable increase in fibroglandular tissue. Radiologists should be aware of the aetiology of such changes, and can obtain information on HRT most conveniently by having the technologist routinely question each patient.     

Effect of x-irradiation, nicotinic acid and neostigmine methylsulfate on the interrelation between methylation and biosynthesis of tRNA

Experiments on rats established that tRNA of the liver under the effect of total X-irradiation (800 R), nicotinic acid and neostigmine methylsulphate proves to be hypermethylated. In this case tRNA molecules undergo conformation changes. Nicotinic acid and neostigmine methylsulphate administered to the animals under experiment an hour before irradiation favour the normalization of these indexes. As a rule, a correlation is observed between changes in methylation of tRNA and activity of their methylases. Irradiation inhibits the processes of tRNA synthesis which are normalized under the effect of nicotinic acid administered before the irradiation. Nicotinic acid and neostigmine methylsulphate produce no effect on synthesis of tRNA in the liver of normal animals. The activity of acid tRNase under the effect of nicotinic acid is not changed, under other conditions of the experiment it decreases. Irradiation against a background of nicotinic acid and neostigmine methylsulphate administered to animals and neostigmine methylsulphate administration to the intact animals inhibit the activity of alkaline tRNase.     

Effects of coca chewing on hormonal and metabolic responses during prolonged submaximal exercise

The effects of coca chewing on prolonged submaximal exercise responses were investigated in chronic coca chewers and compared with a group of nonchewers. At rest, coca chewing during a 1-h period was followed by a significant increase in blood glucose, free fatty acid, and norepinephrine concentrations and a significant reduction in insulin plasma level. During prolonged (1-h) submaximal (65-70% peak O2 uptake) exercise, chewers displayed a significantly greater adrenergic activation (as evidenced by a higher level of plasma epinephrine) and an increased use of fat (as evidenced by a lower respiratory exchange ratio). The gradual increase in oxygen uptake (O2 drift) commonly observed during prolonged exercise was blunted in coca chewers. This blunting in O2 drift is not related to coca-induced changes in ventilatory or lactate responses to exercise but could possible be related to an enhanced glucose utilization by chewers during the late phase of exercise. The present results provide experimental evidence of the physiological effects of coca chewing that could explain the better ability of coca users to sustain strenuous work for an extended period of time.     

Some changes of receptor and postreceptor signal transduction regulated by somatostatin in pituitary hGH-secreting adenomas

OBJECTIVE: To investigate the disturbance in the function of SRIF receptor, Gi protein and Ca2+ channel in hGH adenoma cells and to evaluate their significance in the pathogenesis of pituitary hGH adenomas. METHODS: All 25 patients with pituitary hGH adenoma who were involved in this study had typical acromegalic manifestation and high fasting serum hGH levels of > 5.0 micrograms/L which were not suppressed to < 3.0 micrograms/L by oral glucose tolerance test. The pituitary hGH adenoma tissue obtained from transphenoidal operation was digested by collagenase and the dispersed adenoma cells were cultured in the monolayer. The effects of octreotide (SMS), a long-acting agonist of somatostatin, on hGH secretion and intracellular cAMP level were observed and the influences of pertussis toxin (PT), an inhibitor of Gi protein, and Ca2+ ionophore A23187 or KCl on the inhibitory action of octreotide on hGH secretion were also investigated in the cultured pituitary hGH adenoma cells. RESULTS: A total of 16.0% (4/25) of cultured pituitary hGH adenomas did not respond to octreotide (100 nmol). The inhibitory effect of octreotide on hGH secretion was not blocked by PT (50 ng/ml) and A23187 (10 mumol) or KCl (22.5 nmol) in 31.6% (6/19) and 35% (7/20) of hGH adenomas, respectively. The effects of octreotide on hGH secretion and intracellular cAMP levels were studied in 10 cultured hGH adenomas. Octreotide suppressed both hGH secretion and cAMP levels in 5 cases; inhibited only hGH secretion or the cAMP level in 3 cases and 1 case respectively; and affected neither hGH secretion nor cAMP level in the last case. CONCLUSION: There were abnormalities in the SRIF receptor and/or postreceptor signal transduction in 16.0% of hGH adenomas which did not respond to octreotide. The defects in Gi and/or Ca2+ channels were found in 52.4% (11/21) of hGH adenomas which had responded to octreotide. These defects might induce diminution of the inhibitory action of SRIF on hGH secretion and might be the causes of hypersecretion in some pituitary hGH adenomas.