Interrelationship between serum muscle enzymes and a low T3 in anorexia nervosa

To determine the interrelationship between muscle dysfunction and a low T3 state, both seen in anorexia nervosa, we studied the relationship between the degree of muscle involvement, as assessed by the circulating concentration of the three muscle indicators (CPK, GOT and LDH), and serum T3 in thirty-three patients when they were admitted to the hospital. We also studied the malnutritional state, as assessed by their body weight or serum GH, serum potassium and the degree of hyperactivity exhibited. Additionally, another twelve patients were studied in order to explore the mounding phenomenon which is typically elicited in hypothyroidism. The logarithms of serum CPK and GOT correlated only with the serum T3 concentration (r = -0.35, p less than 0.05; r = -0.41, p less than 0.05; respectively). The logarithm of serum LDH highly correlated with serum T3, the percentage of ideal body weight, and the logarithm of serum GH (r = -0.55, p less than 0.01; r = -0.66, p less than 0.001; r = 0.43, p less than 0.05; respectively). The mounding phenomenon was elicited in ten out of twelve patients. In conclusion, it was implied that a low T3 state was associated with an increase in serum muscle indicators and thus with muscle dysfunction encountered in anorexia nervosa.     

Biochemical values of blood serum in the female silvered leaf-monkey,Presbytis cristatus

Thirteen days after capture, the blood serum of eight anesthetized female leaf-monkeys,Presbytis cristatus (3.86 kg of mean body weight), were analyzed for hematocrit (35.6±6.7 %), total protein (6.7±0.8 g/dl), albumin (3.61±0.77 g/dl), α-1 globulin (0.13±0.04 g/dl), α-2 globulin (0.73±0.18 g/dl), β globulin (0.87±0.27 g/dl), γ globulin (1.36±0.55 g/dl), A/G ratio (1.23±0.38), Na (161±6.14 mEq/l), K (5.61±0.74 mEq/l), LDH (575±257 IU/l), GOT (93±67 IU/l), GPT (34±33 IU/l), CPK (250±200 IU/l), ALP (613±633 IU/l), LAP (115±68 IU/l), γ-GTP (28±30 IU/l), TG (47±24 mg/dl), T-Cho (141±31 mg/dl), BUN (29.0±5.7 mg/dl), T-bil (0.21±0.07 mg/dl), and IP (3.4±2.0 mg/dl).     

Prolactin secretion in patients with idiopathic diabetes insipidus.

It has been demonstrated that hyperprolactinemia is sometimes present even in patients with idiopathic diabetes insipidus (DI). In this study, we examined the responses of serum prolactin (PRL) to hypertonic saline infusion and TRH injection in 11 patients with idiopathic DI diagnosed by clinical examinations. Serum sodium in these patients (147.5 +/- 3.2 mEq/L) was significantly higher at baseline than in normal subjects (139.7 +/- 2.4 mEq/L). The plasma arginine vasopressin (AVP) level was significantly lower in DI (0.42 +/- 0.24 pg/ml) at baseline than in normal subjects (2.53 +/- 1.03 pg/ml). However, the serum PRL level in both groups did not differ significantly except in one patient with idiopathic DI (35.6 ng/ml). There was no significant correlation between the basal serum sodium and basal serum PRL in either group. After an infusion of hypertonic saline, the serum sodium level gradually increased to 155.6 +/- 3.4 mEq/L in DI and to 146.5 +/- 4.3 mEq/L in the normal subjects. However, this increase did not affect PRL secretion in either group. PRL response to TRH was essentially normal in all patients with idiopathic DI. These results indicate that the secretion of PRL is not generally affected by chronic mild hypernatremic hypovolemia in the patients with idiopathic DI.     

Serum aldosterone and protein-binding variables in Yanomama Indians: a no-salt culture as compared to partially acculturated Guaymi Indians

Yanomama Indians from the jungles of southern Venezuela and northern Brazil excreted 1 +/- 1.5 mEq of Na and 203 +/- 109 mEq of K and had low blood pressure (BP), 102/62 mm Hg). In comparison, Guaymi Indians of Panama excreted 103 +/- 50 mEq of Na and 118 +/- 52 mEq of K and had significantly higher BP (114/75 mm Hg, p less than 0.001). Elucidating the renin-aldosterone axis, total upright serum aldosterone in 34 Yanomama was high (85.6 +/- 78 ng/100 ml). The binding capacities of thermolabile (ABG) and thermostable (ABG-Ts) serum globulins for aldosterone were elevated at 23.8 +/- 6 and 14.9 +/- 2.6%, respectively; consequently, total ABG- plus ABG-Ts- bound aldosterone was as high as 38.6 +/- 6.3%. Plasma renin activity (PRA 10.3 +/- 2.4 ng/ml/h) and urinary aldosterone 18-glucuronide (70.3 +/- 30 micrograms/24 h) in 17 Yanomama were also very high. In contrast, total serum corticosteroids and corticosteroid-binding globulin (CBG) binding capacity were normal, suggesting normal ACTH activity. PRA correlated positively with total (r = 0.47, p less than 0.05) and free (r = 0.47, p less than 0.05) serum aldosterone, which in turn showed a negative trend with Na (r = 0.33, NS) excretion. The effect of high dietary K appeared less important to aldosterone stimulation and PRA suppression. ABG-bound aldosterone (r = 0.43, p less than 0.01) as well as ABG-Ts (r = 0.56, p less than 0.05) were negatively correlated with diastolic but not systolic BP. The total ABG- and ABG-Ts-bound fraction correlated with diastolic BP (r = 0.43, p less than 0.05) in contrast to the free fraction (r = 0.08, NS) or total aldosterone (r = -0.09). Apparently, only bound serum aldosterone is important for the maintenance of diastolic BP. High serum aldosterone, with elevated excretion, indicates an increased secretion rate; increased serum protein binding suggests an increased tissular activity and alterations in aldosterone metabolism. In Guaymi Indians both total plasma aldosterone (14.5 +/- 65 ng/100 ml) and urinary aldosterone (8.1 +/- 4.8 micrograms/creatinine excretion) were normal. ABG-binding capacity for aldosterone was moderately elevated (17.8 +/- 4.8) and of ABG-Ts normal (10.2 +/- 1.2) suggesting a nearly normal aldosterone metabolism and regulation. The BP of Guaymi was significantly higher than that of the Yanomama.     

Reduced plasma lipoprotein lipase activity in patients with malignancy-associated weight loss

Post-heparin plasma lipoprotein lipase activity was measured in 28 cancer patients with varying degrees of weight loss, and in 16 normal volunteers. Total lipoprotein lipase activity was decreased by 35.4% (P less than 0.001) in the cancer group. The component lipase activities, hepatic (HLPL), and peripheral (PLPL), were decreased by 40% (P less than 0.001) and 38% (P less than 0.005) respectively. In addition, the level of total peripheral lipoprotein lipase correlated well with the percent body weight lost by these patients (r = 0.6, P less than 0.01). Regardless of extent of disease, patients with lung cancer showed the lowest enzyme activity (mean 191 mU/ml +/- 30 SEM, P less than 0.001) and the greatest percent of weight loss (mean 16%), while patients with breast cancer had nearly normal lipase activity (mean 315 mU/ml +/- 50 SEM, normal 340 mU/ml +/- 22 SEM, P less than 0.10) and minimal weight loss (mean 8.4%). Fasting serum triglycerides were significantly elevated in the patient group (mean 120 mg/dl +/- 9.7 SEM) as compared to normal (mean 71 mg/dl +/- 7 SEM, P less than 0.001). The mean fasting insulin level was elevated in the patient group (13 mU/ml +/- 3.0 SEM), although in the majority of the patients it was found within the normal range (4-24 mU/ml). We conclude that the significant decrease in the total LPL activity may be responsible in part for the characteristic hypertriglyceridemia present in cancer patients.     

The effects of hydrogen peroxide promoted by homocysteine and inherited catalase deficiency on human hypocatalasemic patients

Elevated plasma homocysteine can generate oxygen free radicals and hydrogen peroxide. The enzyme catalase is involved in the protection against hydrogen peroxide. We examined the effect of oxidative stress promoted by homocysteine on erythrocyte metabolism (blood hemoglobin, MCV, folate, B12, serum LDH, LDH isoenzymes, haptoglobin) in the oxidative stress sensitive Hungarian patients with inherited catalase deficiency. The plasma homocysteine (HPLC method, Bio-Rad), folate, B12 (capture binding assay, Abbott), blood hemoglobin concentrations, blood catalase activity (spectrophotometric assay of hydrogen peroxide), and MCV values were determined in 7 hypocatalasemic families including hypocatalasemic (male:12, female:18) patients and their results were compared to those of the normocatalasemic (male:17 female: 12) family members. We found decreased (p <.036) folate (ng/ml) concentrations (male hypocatalasemic 5.44 +/- 2.81 vs. normocatalasemic 7.56 +/- 1.97, female 5.01 +/- 1.93 vs. 6.61 +/- 1.91), blood hemoglobin (p <.010, male:140.2 +/- 11.0 vs. 153.6 +/- 11.6 g/l, female: 128.4 +/- 10.9 vs. 139.6 +/- 9.2 g/l). Increased levels of MCV (p <.001) were detected in hypocatalasemic patients (male: 98.6 +/- 3.4 vs. 90.1 +/- 7.5 fl, female: 95.9 +/- 3.9 vs. 90.1 +/- 2.5 fl), plasma homocysteine (p <.049, male: 9.72 +/- 3.61 vs. 7.36 +/- 2.10 umol/l, female: 9.06 +/- 3.10 vs. 6.84 +/- 2.50 umol/l) and not significant (p >.401) plasma B12 (male: 336 +/- 108 vs. 307 +/- 76 pg/ml, female: 373 +/- 180 vs. 342 +/- 75 pg/ml). The serum markers of hemolysis (LDH, LDH isoenzymes, haptoglobin) did not show significant (p >.228) signs of oxidative erythrocyte damage. We report firstly on increased plasma homocysteine concentrations in inherited catalase deficiency. The increased plasma homocysteine and inherited catalase deficiency together could promote oxidative stress via hydrogen peroxide. The patients with inherited catalase deficiency are more sensitive to oxidative stress of hydrogen peroxide than the normocatalasemic family members. This oxidative stress might be responsible for the decreased concentration of the blood hemoglobin via the oxidation sensitive folate and may contribute to the early development of arteriosclerosis and diabetes in these patients.     

Blood and liver enzymes in rainbow trout (Salmo gairdneri Rich.) with emphasis on their diagnostic use: Study of CCl4 toxicity and a case of Aeromonas infection

The effect of one intraperitoneal injection of 1.33 ml of CCl₄ per kg of fish was studied. Two experimental series were performed and studied for 10 days (with diluent) and 24 h (pure CCl₄) periods. LDH, GOT, GPT, GR, GDH, CPK, G-6-Pase, and AlkPase were studied. The activity of all enzymes in blood increased: LDH (four times the control), GOT (two times), GPT (three times); they reached a maximal activity 12 h after injection of diluted CCl₄. The levels of some enzymes were also examined in the liver. With pure CCl₄, maximal enzyme activity in blood occurred earlier (6 h). A 6 to 10 times increase was observed for GOT, GPT, LDH, GR, and GDH. Histopathological observations were correlated with these enzymes studies.
An Aeromonas disease characterized by the destruction of the dermis, the exposure of the muscle, and by the presence of numerous petechiae in the liver enabled us to examine the relationships between naturally induced tissue damage and enzyme levels in blood. The levels of seven blood enzymes were determined and the most significant modifications were observed for LDH and CPK. which increased their concentration from 3 to 7 times respectively. A pyruvate saturation test demonstrated that LDH was probably from liver as it was observed after CCl₄ poisoning. The contribution of such biochemical studies in fish research is evaluated.     

Circulating factor with ouabain-like immunoreactivity in patients with primary aldosteronism

Circulating factor with ouabain-like immunoreactivity was studied in patients with primary aldosteronism. Anti-ouabain antibody was prepared from specific pathogen-free rabbits. In the plasma of patients with primary aldosteronism, the level of a factor with ouabain-like immunoreactivity was 2.59 +/- 1.39 pmol ouabain equivalent/ml plasma. This value was significantly (p less than 0.05) higher than that of age-matched normotensive subjects, 1.06 +/- 0.86 pmol ouabain equivalent/ml plasma. The plasma level of ouabain-like immunoreactivity correlated significantly (p less than 0.05) with blood pressure. These results indicate that the factor with ouabain-like immunoreactivity may play a pathophysiological role in the maintenance of the high blood pressure observed in patients with primary aldosteronism.     

A threshold exists for the stimulatory effect of insulin on plasma L-carnitine clearance in humans

Maintaining hyperinsulinemia ( approximately 160 mU/l) during steady-state hypercarnitinemia ( approximately 550 mumol/l) increases skeletal muscle total carnitine (TC) content by approximately 15% within 5 h. The aim of the present study was to further examine the relationship between serum insulin concentration and skeletal muscle carnitine accumulation by attempting to identify the serum insulin concentration at which this stimulatory effect of insulin on carnitine retention becomes apparent. On four randomized experimental visits, eight healthy men (body mass index 23.8 +/- 0.9 kg/m(2)) underwent a 6-h euglycemic insulin clamp of 5, 30, 55, or 105 mU x m(-2) x min(-1) accompanied by a 5-h iv infusion of l-carnitine (15 mg/kg bolus followed by 10 mg x kg(-1) x h(-1)). The clamps produced steady-state serum insulin concentrations of 10.1 +/- 0.5, 48.8 +/- 1.0, 88.9 +/- 2.8, and 173.9 +/- 6.5 mU/l, respectively. During l-carnitine infusion, plasma TC concentration remained above 450 mumol/l during all four visits. However, there was a significant treatment effect of insulin (P < 0.001), such that by the end of infusion the plasma TC concentration in the 55- and 105-mU clamps was lower than that seen in the 5- (P < 0.05 and P < 0.01, respectively) and 30-mU (P < 0.01) clamps. The findings demonstrate that only high circulating serum insulin concentrations (> or =90 mU/l) are capable of stimulating skeletal muscle carnitine accumulation. This is of relevance to athletes, and the treatment of obesity and type 2 diabetes, where increasing skeletal muscle carnitine content may be used as tool to modify skeletal muscle energy metabolism.     

Effects of acute intravenous injection of two growth hormone-releasing hormones (GHRH 1-40 and 1-29) on serum growth hormone and other pituitary hormones in short children with pulsatile growth hormone secretion

We administered two different growth hormone-releasing hormones (GHRH) to 20 short, prepubertal children who had spontaneous secretion of growth hormone (GH), assessed from 24-hour GH secretion profiles (72 sampling periods of 20 min). We compared one i.v. injection of 1 microgram/kg of GHRH 1-40 with that of GHRH 1-29 regarding serum concentrations of GH, prolactin, luteinizing hormone, follicle-stimulating hormone and IGF-I. The children were allocated to two groups without statistical randomization. Both groups were given both peptides, with at least 1 week in between. The first group started with GHRH 1-40, the other with GHRH 1-29. The peptides both induced an increased serum concentration of GH of the same magnitude: mean maximal peak of 89 +/- 12 mU/l after GHRH 1-40 and 94 +/- 10 mU/l after GHRH 1-29 (n.s.). The mean difference in maximum serum GH concentration in each child after injection was 52 +/- 9 mU/l, range 1-153 mU/l. GHRH 1-29 also induced a short-term, small increase in the concentrations of prolactin (p less than 0.05), luteinizing hormone (p less than 0.01) and follicle-stimulating hormone (p less than 0.05). We conclude that the shorter sequence GHRH 1-29, when given in a dose of 1 microgram/kg, gives a rise in serum concentration of GH similar to that after the native form GHRH 1-40.     

Serum enzyme variations in men during an exhaustive "square-wave" endurance exercise test

The present study was designed to test if both the intensity and duration of the 45-min Square-Wave Endurance Exercise Test (SWEET) would produce changes in serum enzyme activities. Nine men, four sedentary (S) and five athletes (A), performed VO2 max and SWEET, at their Maximal Intensity of Endurance (MIE45) as defined by maximal heart rate and the impossibility of maintaining MIE 45 + 5% for 45 min. Arterial blood was sampled at rest (R), exercise (Ex) (45th min) and during recovery (15th min) for measurements of levels of Haemoglobin (Hb), Haematocrit (Hct), pH and seven serum enzymes: Creatine kinase (CPK), Hexose-phosphate isomerase (PHI), Aldolase (ALD), Lactate dehydrogenase (LDH), Malate dehydrogenase (MDH), Aspartate amino-transferase (ASAT or GOT), and Alanine aminotransferase (ALAT or GPT). Five enzymes increased significantly during exercise (MIE45), the delta % (Ex - R/R) increases were as follows: PHI (72%), MDH (28%), LDH (21%), CPK (17%), and GOT (13.5%), whilst only a 10% increase was observed for Hct and Hb and there was no significant change in the arterial pH. There was no correlation between the delta % of Hb, Hct, pH, and the results for the enzymes. Thus, it does not seem that haemoconcentration and arterial blood acidosis which occur during exercise are only at the origin of the observed increases in enzymes. A difference between "sedentary" and "athletes" subjects was found at rest and exercise (delta % = A - S/S) for CPK (R = 222%; Ex = 235%), GOT (R = 90%; Ex = 75%) and ALD (R = 99%; Ex = 54%). These results suggest that the MIE45, by measured increases in enzymatic activity, seems to require great muscular effort.     

Sperm creatine phosphokinase activity as a measure of sperm quality in normospermic, variablespermic, and oligospermic men

We have found a significant inverse correlation between sperm concentrations and sperm creatine N-phosphotransferase (CPK) activities in oligospermic and normospermic human specimens. In the present work, we carried out serial CPK determinations to assess whether there is a relationship between fluctuating sperm concentrations and sperm quality in consistently oligospermic and variablespermic (sperm concentrations are occasionally in the greater than 20 million/ml range) husbands of 65 couples (23 normospermic men/51 samples, 25 consistently oligospermic men/80 samples, and 17 variablespermic men/68 samples). The sperm CPK activities were significantly lower in the normospermic vs. the oligospermic or variablespermic groups (p less than 0.001), but there were no differences between the latter two (p greater than 0.25). The mean CPK values of migrated sperm fractions in both the oligospermic and variablespermic populations were improved (at least 20% decline in CPK values) compared to those of the initial specimens (1.27 +/- 0.38 vs. 0.68 +/- 0.37 and 0.77 +/- 0.32 vs. 0.46 +/- 0.24 SEM U/100 million sperm, respectively, p less than 0.001 in both pairs) and the incidence of the "failed-to-improve" samples was also similar in the two groups (44/36 vs. 45/23, p greater than 0.2). The lack of differences in the mean CPK activities, in the distribution of CPK values under and over 0.250 U/100 million sperm level, and in the ratio of migrated samples with improved or with failed-to-improve CPK activities suggests that sperm quality is not different between men who are consistently oligospermic and those who occasionally produce normospermic specimens.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hepatic dysfunction in primary hypothyroidism

Twenty-seven patients with primary hypothyroidism were studied to evaluate the relationship between hepatic function and thyroid hormone deficiency in this disorder. In hypothyroidism, hypergammaglobulinemia was found in 71%, elevated glutamic oxaloacetic transaminase (GOT) in 48%, high lactic dehydrogenase (LDH) in 58%, hypercholesteremia in 52% and low elimination rate constant of indocyanin green (KICG) in 44%. In each criterion of liver function, these patients were divided into two groups, normal level and abnormal level group, respectively. T3 and T4 in patients with abnormal levels of GOT, glutamic pyruvic transaminase (GPT), gamma-glutamyl transpeptidase (gamma-GTP), leucine aminopeptidase (LAP), alkaline phosphatase (ALP) and 45 minutes retention rate of bromsulphalein (BSP) were not different from those in the normal level group. However, T3 and T4 in patients with abnormal levels of LDH, cholesterol, cholinesterase (ChE) and KICG were lower than those in the normal level group. The abnormal KICG group had a statistically higher cardio-thoracic ratio (CTR) than the normal group (65.7 +/- 18.8% vs 50.4 +/- 8.3%, p less than 0.05). In patients with pericardial effusion, CTR was 65.9 +/- 14.6%, while that in patients without pericardial effusion was 49.9 +/- 7.5% (p less than 0.05). These abnormalities of liver function were normalized in all cases after hormone replacement therapy. Liver biopsy in three cases disclosed normal liver in two cases and mild infiltration of monocyte into Glisson's capsule in one case.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hyponatremia-induced brain edema in guinea pigs is reduced by treatment with the novel anion transport inhibitor L-644,711

Cerebral edema in various disease states may result from astroglial swelling due to increased NaCl uptake mediated by enhanced Cl-HC03 exchange. We evaluated this mechanism in the pathogenesis of cerebral edema in acute hyponatremia by administering L-644,711, a fluorenyloxyacetate derivative that functions as an anion exchange inhibitor, to guinea pigs with severe reductions in serum Na+ concentration. Acute hyponatremia was induced for 54 hr by daily injections of arginine vasopressin (10 U/day) and 5% dextrose in water (7.5% body wt/day). Experimental animals received L-644,711, 20 mg/kg/day, while controls were given an equal volume of the diluent. This regimen lowered the serum Na from normal levels to 108 +/- 3 and 109 +/- 4 mM in experimental and control animals, respectively. Drug treatment resulted in less cerebral edema characterized by a reduction in brain total tissue water 432 +/- 4 vs 466 +/- 8 ml/100 g dry wt experimental vs control, P less than 0.005. This difference was composed mainly of less expansion of the intracellular water space, 287 +/- 11 vs 323 +/- 9 ml/100 g dry wt experimental vs control, p less than 0.005. The cerebral cortical Na+ +Cl content was reduced from 55.5 +/- 1.3 (control) to 39.5 +/- 1.1 mEq/100 g dry wt (experimental), p less than 0.01. These results indicate that treatment of guinea pigs with L-644,711 decreases brain NaCl content and attenuates cerebral edema during severe acute hyponatremia without normalizing the serum Na+ concentration.     

Angiotensin-converting enzyme and anorexia nervosa

Angiotensin-converting enzyme (ACE) activity was measured in 10 patients with anorexia nervosa, 6 with hyperthyroid Graves' disease, and 7 with primary hypothyroidism. Patients with anorexia nervosa had a low serum ACE activity (9.8 +/- 2.2 IU/l), as compared to findings in normal subjects (13.4 +/- 3.5 IU/l) (P less than 0.05). Patients with hyperthyroid Graves' disease had high serum ACE activity (23.7 +/- 5.8 IU/l), as compared to levels in normal subjects (P less than 0.01), and patients with primary hypothyroidism tended to have low serum ACE activity (10.1 +/- 1.8 IU/l), compared to the normal subjects (P less than 0.1). Following weight gain (before; 71.3 +/- 10.2% of ideal body weight, after; 88.7 +/- 5.6% of ideal body weight), serum ACE activity in patients with anorexia nervosa reverted to within the normal range (13.8 +/- 3.5 IU/l), and serum T3 concentration was restored to the normal range (before; 0.7 +/- 0.2 ng/ml, after; 1.1 +/- 0.3 ng/ml). In these patients, ACE activity correlated with the per cent of ideal body weight (P less than 0.05). These data suggest that, in underweight subjects with anorexia nervosa, decreased serum ACE activities may relate to emaciation.     

Na-dependent changes in intracellular Ca in spontaneously hypertensive rat hearts.

To determine whether Na/Ca exchange is altered in primary hypertension, Na-dependent changes in intracellular Ca, ([Ca]i), were measured in isolated perfused hearts from Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Intracellular Na, (Nai, mEq/kg dry wt), and [Ca]i were measured by NMR spectroscopy. Control [Ca]i was less in WKY than SHR (176 +/- 18 vs 253 +/- 21 nmol/l; mean +/- S.E., P < 0.05), whereas Nai was not significantly different. One explanation for this is that net Na/Ca exchange flux is decreased in SHR. If this hypothesis is correct, the rate of Ca uptake in SHR should be less than WKY when Na/Ca exchange is reversed by decreasing the transmembrane Na gradient. The Na gradient was reduced by decreasing extracellular Na, ([Na]o) and/or by increasing [Na]i. To increase [Na]i, Na uptake was stimulated by acidification while Na extrusion by Na/K ATPase was inhibited by K-free perfusion. Seventeen minutes after acidification, Nai had increased but was not significantly different in SHR and WKY (18.0 +/- 2.3 to 57.4 +/- 7.6 vs 20.3 +/- 0.6 to 66.5 +/- 4.8 mEq/kg dry wt, respectively). Yet [Ca]i was greater in WKY than SHR (1768 +/- 142 vs 1201 +/- 90 nmol/l; P < 0.05). [Ca]i was also measured after decreasing [Na]o from 141 to 30 mmol/l. Fifteen minutes after reducing [Na]o, [Ca]i was greater in WKY than SHR (833 +/- 119 vs 425 +/- 94 nmol/l; P < 0.05). Thus for both protocols, decreasing the transmembrane Na gradient led to increased [Ca]i in both SHR and WKY, but less increase in SHR. The results are consistent with the hypothesis that Na/Ca exchange activity is less in SHR than WKY myocardium.     

Decrease of erythropoietin level by human recombinant tumour necrosis factor alpha (hrec TNFalpha) in patients with advanced cancer

Anaemia is a frequent complication of chronic inflammation, infectious diseases and cancer. Inappropriate erythropoietin production is regarded as one of the main causative factors responsible for the occurrence of anaemia. The pathogenesis of TNFalpha induced-anaemia has not been fully clarified yet and its influence on hematopoiesis has been suggested. We performed a clinical study to access the influence of hrec TNFalpha administration on plasma EPO concentration and the degree of anaemia in patients with advanced solid tumours for whom no other kind of therapy but palliative treatment was available. All these patients exposed mild anaemia (HT 36.1 +/- 1.0%). Plasma EPO was estimated at 8 a.m. before and after 5 days of TNFalpha therapy with a dose of 75 pg/day iv (cycle I). Two weeks later plasma EPO was estimated again before and after 5 days of TNFalpha administration of a double dose (150 microg/day) (cycle II). The control group comprised 8 non-cancer patients (5M/3F, age 48.5 +/- 6yr) with the same degree of anaemia (HT 36 +/- 1.1%) due to haemorrhage. In the control group the plasma EPO level was significantly higher (54.2 +/- 8 mU/ml) than in cancer patients before cycle I (17.1 +/- 2.5 mU/ml) and II (14.6 +/- 3.8 mU/ml) respectively.TNF administration was followed by a significant decline of plasma EPO both after the first (17.1 +/- 2.5 vs 9.0 +/- 1.5 mU/ml) and second cycle (14.6 +/- 3.8 vs 8.4 +/- 2.0 mU/ml) of TNF treatment. CONCLUSIONS: Patients with solid cancer and mild anaemia are characterised by inappropriate low plasma EPO concentration. Therapy with TNFalpha exerts a suppressive effect on EPO secretion in these patients.     

Cardiac sensitivity to hyperkalemia in adrenalectomized dogs.

In dogs with bilateral adrenalectomy loaded with K by infusion of 2 mEq KCI/kg/hr there is a marked increase of cardiac sensitivity to hyperkalemia. Typical ECG changes begin at lower serum K levels (5-6 mEq/l) and the prelethal arrhythmias that signal the imminent onset of fatal when mean serum K is 7.6 mEq/l, 2.9 mEq/l above the average pre-infusion level. In control dogs, ECG changes start above 8 mEq K/liter, and prelethal arrhythmias appear between 9.5 and 10.2 mEq/l, a mean increase of 5.6 mEq/l above the average preinfusion level.     

Prediction of physical performance through muscle enzymes activity

Physical performance deteriorates during strenuous exercise as manifested by a decrease in maximal aerobic power and increased activity of serum muscle enzymes. The relationship between these parameters was investigated in 41 trained subjects during 24 h marches and the following recovery period. Peak O2 uptake and serum activity of creatine phosphokinase (CPK) and glutamic oxalacetic transaminase (GOT) were measured. During the marches there was a simultaneous, significant elevation in serum CPK and GOT activity and a significant reduction in peak O2 uptake. During the early recovery period (24 h) no significant changes occurred in muscle enzyme activity and peak O2 uptake; thereafter (up to 72 h after the end of the march), a gradual decline in enzyme activity levels with a concomitant increase in peak O2 uptake was observed, reaching pre-march values. A "mirror image" relationship between muscle enzyme activity and peak O2 uptake was found during three clearly distinguished phases: a) 24 h march, b) early recovery stage and c) late recovery stage. These findings suggest that muscle enzyme leakage from muscle cells is closely related to the decline in muscular function and aerobic power. Thus, muscle enzyme activity might be a practical measure of physical performance capacity during the early and late stages of recovery from prolonged endurance exercise.     

Direct assessment of muscle glycogen storage after mixed meals in normal and type 2 diabetic subjects

To understand the day-to-day pathophysiology of impaired muscle glycogen storage in type 2 diabetes, glycogen concentrations were measured before and after the consumption of sequential mixed meals (breakfast: 190.5 g carbohydrate, 41.0 g fat, 28.8 g protein, 1253 kcal; lunch: 203.3 g carbohydrate, 48.1 g fat, 44.0 g protein, 1497.5 kcal) by use of natural abundance (13)C magnetic resonance spectroscopy. Subjects with diet-controlled type 2 diabetes (n = 9) and age- and body mass index-matched nondiabetic controls (n = 9) were studied. Mean fasting gastrocnemius glycogen concentration was significantly lower in the diabetic group (57.1 +/- 3.6 vs. 68.9 +/- 4.1 mmol/l; P < 0.05). After the first meal, mean glycogen concentration in the control group rose significantly from basal (97.1 +/- 7.0 mmol/l at 240 min; P = 0.005). After the second meal, the high level of muscle glycogen concentration in the control group was maintained, with a further rise to 108.0 +/- 11.6 mmol/l by 480 min. In the diabetic group, the postprandial rise was markedly lower than that of the control group (65.9 +/- 5.2 mmol/l at 240 min, P < 0.005, and 70.8 +/- 6.7 mmol/l at 480 min, P = 0.01) despite considerably greater serum insulin levels (752.0 +/- 109.0 vs. 372.3 +/- 78.2 pmol/l at 300 min, P = 0.013). This was associated with a significantly greater postprandial hyperglycemia (10.8 +/- 1.3 vs. 5.3 +/- 0.2 mmol/l at 240 min, P < 0.005). Basal muscle glycogen concentration correlated inversely with fasting blood glucose (r = -0.55, P < 0.02) and fasting serum insulin (r = -0.57, P < 0.02). The increment in muscle glycogen correlated with initial increment in serum insulin only in the control group (r = 0.87, P < 0.002). This study quantitates for the first time the subnormal basal muscle glycogen concentration and the inadequate glycogen storage after meals in type 2 diabetes.