Alpha 1-adrenergic stimulation of ketogenesis and fatty acid oxidation is associated with inhibition of lipogenesis in rat hepatocytes

The effect of norepinephrine on fatty acid synthesis (3H2O incorporation into fatty acids), on fatty acid oxidation to CO2 and on ketogenesis was studied in isolated hepatocytes of fed rats. After incubation with norepinephrine (50 microM), lipogenesis was lower (5.7 +/- 1.1 nmoles 3H2O incorporated into fatty acids/mg dry weight/30 min) than in controls (7.5 +/- 1.7; n = 6, p less than 0.02). In contrast, (1-14C) palmitate conversion into total ketone bodies was increased to 10.9 +/- 1.8 nmoles/mg/30 min with norepinephrine, vs 8.5 +/- 1.6 in controls (p less than 0.05), and more (1-14C) palmitate was converted to 14CO2 with norepinephrine than in controls (1.48 +/- 0.10 nmoles/mg/30 min vs 1.06 +/- 0.11, p less than 0.05). The inhibitory effect of norepinephrine on lipogenesis was abolished by addition of the alpha 1-receptor blocker prazosin, but not by alpha 2 or beta-blockers. The results demonstrate that the ketogenic effect of norepinephrine is coupled with an inhibitory effect on lipogenesis which may be explained by diminished activity of acetyl-CoA carboxylase, diminished formation of malonyl-CoA and decreased activity of carnitine palmitoyl transferase I.     

Plasma estrogens in Pleurodeles waltlii. Comparison between diploid and triploid females]

Estrogens have been examined in the plasma of diploid and triploid newts Pleurodeles waltlii. Estradiol-17 beta (E2) and estrone (E1) were determined by radioimmunoassay, before and after enzymatic hydrolysis of the conjugates. Total (t) and unconjugated (u) E2 levels were positively correlated (E2u = 0.478 35 E2t + 0.579 98; r = 0.883), but no correlation was detected between E1 levels. No statistical difference was found for the estrogen levels between the different experimental lots of diploid newts (E2t = 7.5 +/- 0.37 ng/ml, E2u = 4.3 +/- 0.20 ng/ml, E1t = 2.19 +/- 0.08 ng/ml, E1t = 0.41 +/- 0.02 ng/ml) but every estrogen level was lower in the triploid group (E2t = 1.8 +/- 0.60, E2u = 1.0 +/- 0.18, E1t = 1.4 +/- 0.13, E1u = 0.3 +/- 0.04 ng/ml). This difference is discussed in relation to lower fertility of the triploid females.     

Comparison of X-prolyl dipeptidyl-aminopeptidase activity in human cerebrospinal fluid with that in serum

Summary X-Prolyl dipeptidyl-aminopeptidase activities in cerebrospinal fluid and serum from the same patients without neurological diseases, undergoing surgery under lumbar anesthesia, were assayed fluorometrically with a newly synthesized fluorogenic substrate, 7-glycylproline-4-methylcoumarinamide; the values were 129.1±19.5 nmoles/min/1 and 54.17±3.11 moles/min/1 (mean±SEM, n=23), respectively, and there was no correlation between both activities (r=0.0894).     

A tonic component in the motility of the upper urinary tract (renal pelvis-ureter)

In isolated muscle strips of porcine renal pelvis and ureter, the calcium antagonist nifedipine (3.10(-7) moles/l) completely suppressed spontaneous phasic mechanical activity and the phasic components of an adrenaline-induced activation (P-component). In the presence of nifedipine, adrenaline induced in pelvis preparations (but not in the ureter) a tonic contraction (T-component) which was on average 61% of the control reaction (SD +/- 26%; n = 35).     

4-Proline and 4-hydroxyproline analogs of arginine vasopressin: role of the proline substitution in the two beta-turns of vasopressin

[4-L-Proline]arginine vasopressin, [4-D-proline]arginine vasopressin, [4-hydroxyproline]arginine vasopressin and [4-proline, 7-hydroxyproline] arginine vasopressin were synthesized and found to have antidiuretic activities of 91 +/- 4, 1.7 +/- 0.2, 1.0 +/- 0.1 and 4.4 +/- 1.0 units/mg, respectively. None of these analogs exhibited a significant level of rat pressor activity. The observed activities of these and other analogs with substitutions at position 4 and/or 7 are discussed on the basis of hypotheses and data bearing on the solution conformation of vasopressins.     

High K+-induced release of somatostatin from the cortical preparation of rat brain.

Release of endogenous somatostatin (SRIF) from the rat cerebral cortical slices incubated in Krebs-bicarbonate buffer was increased from the basal rate of 3.4 +/- 0.6% of the total SRIF content in 15 min at [K+]o = 5.6 mM, to 13.1 +/- 1.6% upon raising the [K+]o to 56.6 mM. The high-K+ evoked SRIF release was absent when Ca++ in the medium was replaced by Mn++. The isolated synaptosomes from rat cerebral cortex contain 13.2 +/- 3.1 ng SRIF/mg protein compared to 0.33 +/- 0.01 ng/mg protein in the cortical tissue as a whole, suggesting that nerve terminals are the main source of the peptide released upon membrane depolarization.     

Chromosome aberrations,micronuclei, and activity of superoxide dismutases in human lymphocytes after irradiation in vitro

The goal of this study was to provide data on the dose-dependent production of dicentrics and micronuclei in human lymphocytes irradiated with 22.6 MeV protons and to estimate the possible contribution of intracellular superoxide dismutases (SOD) to the relative biological effectiveness (RBE) of protons. For the dose-response study, heparinized whole blood of a healthy volunteer was irradiated with protons and X-rays employing radiation doses of 0.5-4 Gy. Three biological endpoints were analyzed: chromosomal aberrations, micronuclei, and specific activity of cytosolic (CuZnSOD) and mitochondrial (MnSOD) superoxide dismutases in harvested human blood cells. Dicentric dose-response curves fit a linear-quadratic form (alpha = 0.094 +/- 0.006, beta = 0.032 +/- 0.001) induced with X-rays and (alpha = 0.119 +/- 0.057, beta = 0.029 +/- 0.014) for 22.6 MeV protons. Protons were more effective than X-rays in producing exchanges, particularly at 0.5 and 1 Gy. In contrast to X-ray irradiated samples where a significant increase in the specific activity of MnSOD was recorded (up to a radiation dose of 1 Gy), irradiation with protons markedly reduced its activity. As a consequence of the reduced activity of MnSOD, the chromosomal dose-response curve became quadratic. The RBE for dicentrics varies with dose (from 2.2 to 1.01) and reduced activity of MnSOD is an important contributor to the RBE of protons. SODs, particularly MnSOD, play an important role in defending DNA from reactive oxygen species. A reduced activity of SOD, particularly MnSOD, is an important contributor to the RBE of protons.     

Isoguvacine, isonipecotic acid, muscimol and N-methyl isoguvacine on the GABA receptor in rat sympathetic ganglia.

The GABA-mimetic activities of 4 analogues muscimol, isonipecotic acid, isoguvacine and N-methyl isoguvacine have been examined at the GABA receptor in the rat isolated superior cervical ganglion. The depolarizing action of all 4 analogues could be selectively antagonized by bicuculline methochloride and isopropyl bicyclophosphate. Muscimol was the only analogue more potent than GABA (molar potency ratio = 5.08 +/- 0.707). The potency of isoguvacine was 0.23 +/- 0.026 and isonipecotic acid 0.011 +/- 0.0028. N-methyl isoguvacine was less than 0.001 GABA.     

Time and theophylline influence on the quantitative variations of the glomerular basement membrane ferritin pathway (author's transl)

A fine quantitative evaluation of ferritin aggregates in rat GBM permits to counts 5.08 +/- 1.51 and 18.30 +/- 3.21 g/cm2, respectively 30 and 60 min after ferritin injection; likewise, 30 min after ferritin administration, 5.08 +/- 1.51 and 17.11 +/- 3.9 g/cm2, respectively in normal and theophylline-treated animals.     

Effects of blood sampling, anesthesia and surgery on plasma vasopressin concentration in rats.

The influence of blood sampling, anesthesia and surgery on plasma vasopressin concentration was assessed in rats. Mean plasma concentration in conscious, chronically catheterized rats was 1.4 +/- 0.1 pg/ml (n = 6). This value remained constant over repeated plasma samplings in the same animals. On the other hand, decapitation increased the plasma vasopressin concentration to 6.0 +/- 2.4 (in pg/ml) (n = 6), inactin anesthesia to 2.9 +/- 0.6 (n = 6), anesthesia and femoral cannulation to 13.3 +/- 5.8 (n = 6) and surgery for renal micropuncture to 81.3 +/- 35.0 (n = 6). It is concluded that the level of circulating plasma vasopressin is highly dependent on the sampling technique and is closely related to the extent of surgery.     

Capillary blood flow in the testes and testosterone secretion in the starved rat

Summary The average capillary blood flow in the testes was found to be 181 l/min/g testis tissue (n=19) in rats starved for 5 days and 273 l/min/g (n=18, p<0.01) in the control group. Plasma testosterone was significantly decreased in the starved animals (1.00±0.06 ng/ml vs 5.43±0.63 ng/ml). When starved and control rats were stimulated with human chorion gonadotropin, testosterone values in plasma were greatly increased in both groups. The capillary blood flow was not altered. The data indicate that human chorion gonadotropin can stimulate testosterone production in the starved rat without influencing the reduced capillary blood flow.     

Human growth hormone in urine: development of an ultrasensitive radiometric assay

An immunoradiometric assay for human growth hormone (HGH) has been developed which has a detection limit of 1 ng/l and can measure HGH in unextracted urine from normal children and adults. The assay is based on a two-step procedure, using a solid-phase goat-anti-HGH immunosorbent for immunoextraction and [125I]-labeled monoclonal HGH-antibody for detection and quantification. The assay is not affected by urea, NaCl or changes of pH from 5-8. The mean urine HGH concentration in normal children is 6.78 +/- 7.6 (SD) pg/ml, in patients with HGH-deficiency 1.3 +/- 0.9 pg/ml which increases to 11.7 +/- 13.4 pg/ml on the day of growth hormone injection.     

Effects of 18-hydroxydeoxycorticosterone on central nervous system excitability

The effects of 18-hydroxydeoxycorticosterone (18-OH-DOC) on central nervous system excitability were studied in adrenalectomized rats. Sixty-four evoked potentials (EP) recorded from the pontine reticular formation were averaged before and after the injection of vehicle and hormone. 750 micrograms of 18-OH-DOC dissolved in 0.5 ml of a 4:1 saline Cremophor-EL solution were injected i.v. A decrease of 55.7 +/- 6.1% in the amplitude of the EPs was observed with the hormone 16.3 min +/- 2.7 (SE) after injection. Amplitude values returned to baseline levels 38 min +/- 6.8 (SE) after injection. The secretion of 18-OH-DOC is greatly increased by ACTH and might modulate central nervous system function.     

Determination of rubidium in human serum

Field desorption mass spectrometry (FD-MS) combined with stable isotope dilution has been used to determine rubidium concentrations from human serum. Samples obtained from 110 healthy volunteers (50 males, 60 females) were examined. The rubidium concentrations found varied from 0.96 to 3.56 mumoles/l, the average value being 1.96 mumoles/l. The precision of the measurements within a batch was 0.8%. The time for 1 analysis, including sample preparation is about 30 min, the total sample consumption is 100-200 mul. The corresponding potassium concentrations were also determined from all these serum samples; a weak trend towards higher potassium levels with increasing rubidium concentration is found.     

Identification of calcium antagonist receptor binding sites using (3H)nitrendipine in bovine tracheal smooth muscle membranes

(3H)Nitrendipine binding to the bovine tracheal muscle membrane at 25 degrees C was rapid, saturable (Bmax = 14.8 +/- 3.9 fmol/mg protein) and of high affinity (Kd = 0.15 +/- 0.04 nM). The rank order of Ca2+ antagonists competing for airway (3H)nitrendipine binding was nitrendipine not equal to nisoldipine not equal to nifedipine much greater than verapamil. Cromolyn, however, neither inhibited nor increased the binding.     

Effect of hyperkalemia on insulin secretion

The effect of hyperkalemia on insulin secretion remains undefined. We evaluated portal and peripheral insulin levels in anesthetized dogs after infusions of KCl. The mean maximal increase in peripheral plasma potassium at infusion rates of 0.2 mEq/kg/h was 0.68 +/- 0.20 mEq/l. There were no significant increases in either portal or peripheral insulin levels. In contrast, in six dogs whose plasma potassium concentration increased in each case by more than 2.0 mEq/l (infusion rate of 0.5 mEq/kg/h), portal insulin levels increased fivefold (p less than 0.05). We concluded that only marked increases in plasma potassium concentration stimulate pancreatic insulin secretion.     

Interaction of cortisol and epinephrine in the regulation of leucine kinetics in man

To assess the interaction of the two major stress hormones epinephrine and cortisol in the regulation of leucine kinetics in man, epinephrine (50 ng/kg/min) was infused either alone or in combination with cortisol (2 micrograms/kg/min) into two groups of 6 postabsorptive normal male subjects during 180 min. Plasma leucine concentrations decreased by 28% (p less than 0.05) from baseline during epinephrine treatment (plasma levels 515 pg/ml); this was due to a decrease of leucine appearance (determined by 1-13C-leucine infusions) by 23% (p less than 0.025); leucine oxidation decreased by 29% (p less than 0.05). However, when plasma cortisol concentrations were elevated to supraphysiological levels (16.3 mumol/l) during epinephrine administration, the decreases of leucine plasma concentrations, appearance and oxidation were abolished. Plasma glucose and FFA concentrations were similarly elevated during both kinds of treatment. Since leucine appearance represents a measurement of total body protein breakdown and leucine disappearance into non-oxidative pathways reflects protein synthesis, the data indicate that plasma epinephrine concentrations during severe stress exert a protein anabolic effect in man which may counteract catabolic properties of elevated plasma cortisol.     

Age distribution of circulating alpha-interferon

A sensitive radioimmunoassay showed that circulating alpha-interferon in the plasma of healthy individuals was low in children and reached the highest level in the young adult, then declined gradually with age. Circulating alpha-interferon was 0.201 +/- 0.059 ng/ml in males (n = 19) and 0.184 +/- 0.076 ng/ml in females (n = 14) at ages 30-39 years old. It was noted that circulating alpha-interferon was maintained up to a certain level even in elderly individuals.     

Adrenocortical metabolism and plasma corticosterone in soman intoxicated rabbits

The organophosphate neurotoxin soman produced impairments in adrenocortical RNA and protein metabolism. Fasciculate and reticular cell RNA and protein contents were suppressed with sublethal to acutely lethal dosages (20, 30 and 40 micrograms/kg, s.c.) during the acute excitatory phase of intoxication and at 6-8 h post injection. All three dosages produced ca 90% inactivation of plasma cholinesterase. A transient elevation of plasma corticosterone occurred with 20 micrograms/kg soman whereas there was a protracted increase with 30 micrograms/kg. Corticosterone was not significantly elevated with 40 micrograms/kg, but death occurred at 13 +/- 4 min. Thus, the magnitude and/or nature of soman-induced metabolic impairments does not appear to prevent adrenal activation.     

Neuropeptide Y in the guinea-pig biliary tract

High concentrations of neuropeptide Y (NPY) have been demonstrated in the gall bladder (16.7 +/- 5.4 pmol/g), cystic duct (25.4 +/- 9.2 pmol/g) and common bile duct (54.7 +/- 11.5 pmol/g) of the guinea-pig using a recently developed radioimmunoassay. Immunoreactive NPY containing nerves were demonstrated in all layers of the biliary tree using immunocytochemistry, being particularly dense in the myenteric and mucosal plexuses.