Respective Control Values Research Articles

Sympathetic Muscle Nerve Activity, Peripheral Blood Flows, and Baroreceptor Reflexes in Humans during Propofol Anesthesia and Surgery

With percutaneous recordings of muscle nerve sympathetic activity (MSA), it is possible to study interactions between the autonomic nervous system and anesthetics. This study describes the effects of propofol infusion both before and during microlaryngoscopy. Nine patients participated. MSA was recorded, muscle and skin blood flows were measured. Sodium nitroprusside-induced decreases in blood pressure were used to quantitate baroreceptor reflex sensitivity. During steady state propofol anesthesia (0.1 mg.kg-1.min-1), "total MSA" (MSA burst area per minute) was 37% (P < 0.05) of awake control value; leg blood flow recorded by strain-gauge plethysmography was 227% (difference not significant); and skin blood flow recorded by laser Doppler flowmetry and finger pulse plethysmography was 300% (P < 0.05) and 376% (P < 0.05) of respective awake control values. During microlaryngoscopy, when mean arterial blood pressure was controlled as close as possible to mean arterial blood pressure in the awake state by individually adjusted propofol infusion rates (average 0.33 mg.kg-1.min-1) MSA was restored to 93% of the activity before anesthesia, and leg blood flow increased further. Both cardiac and muscle sympathetic baroreflex sensitivities were depressed by propofol. During surgery the cardiac baroreflex sensitivity decreased further, whereas the muscle sympathetic baroreflex sensitivity was unchanged. Propofol is a potent inhibitor of sympathetic neuronal activity and decreases the sensitivity of the baroreflex. When used to control the pressor response during surgery, the vasodilatating effect of propofol overrides the neural vasoconstriction induced by surgery, and a further inhibition of the cardiac baroreflex is observed.

Protective effect of Artemisia scoparia extract against acetaminophen-induced hepatotoxicity

1. 1. Hepatoprotective activity of hydro-methanolic extract of Artemisia scoparia (Compositae) was investigated against acetaminophen-induced hepatic damage. 2. 2. Acetaminophen at a dose of 1 g/kg produced 100% mortality in mice while pretreatment of animals with plant extract (150 mg/kg) reduced the death rate to 20%. 3. 3. Acetaminophen at a dose of 640 mg/kg produced liver damage in rats as manifested by the rise in serum levels of GOT and GPT to 1528 ± 310 and 904 ± 261 IU/l ( n = 10) respectively, compared to respective control values of 80 ± 11 and 38 ± 09. 4. 4. Pretreatment of rats with plant extract (150 mg/kg) lowered significantly the respective serum GOT and GPT levels to 85 ± 11 and 23 ± 06. 5. 5. These results indicate that Artemisia scoparia contains hepatoprotective constituents and this study rationalizes the traditional use of this plant in hepatobiliary disorders.

Contractile properties of skinned fibers from hypertrophied skeletal muscle

We have previously shown deficits in specific tension (N.cm-2) in whole hypertrophied skeletal muscle (18-30%). The purpose of the present study was to determine if this intrinsic deficit exists in chemically skinned, hypertrophied single fibers, and also to measure their Ca2+ sensitivity. One group of rats (N = 4) had bilateral surgical ablation of the gastrocnemius and soleus muscles, and another group (N = 4) had the gastrocnemius and plantaris muscles ablated to induce hypertrophy in the plantaris and soleus muscles, respectively. Thirty days after surgery five fibers were dissected and analyzed from each of eight muscles per group, including control muscles. In hypertrophied plantaris and soleus muscles, fiber cross-sectional area (CSA) was 20% and 29% greater, respectively, than control values. Maximal Ca2+ activated tension (Po, pCa 4.5) was 15% greater in hypertrophied plantaris fibers and 18% greater in hypertrophied soleus fibers compared with respective control values (P < 0.05). Therefore, Po expressed per fiber CSA was slightly depressed (3-8%) in both plantaris and soleus fibers (P < 0.05). Regarding Ca2+ sensitivity, the Ca2+ concentration to elicit 50% of Po (i.e., pCa50) was significantly lower in hypertrophied soleus (58%) and plantaris (29%) fibers. This leftward shift in the force-pCa curve reflects greater Ca2+ sensitivity in hypertrophied fibers. Since the single fiber Po/CSA was only slightly decreased, these data suggest that during tetanic stimulation of whole muscle Ca2+ delivery to the contractile apparatus may be impaired.(ABSTRACT TRUNCATED AT 250 WORDS)

SUBCHRONIC TOXICITY STUDY OF EASTERN BLACK NIGHTSHADE (SOLANUM PTYCANTHUM) BERRIES IN SPRAGUE‐DAWLEY RATS

ABSTRACT Species of the Solanum nigrum complex, including eastern black nightshade (S. ptycanthum Dun.), are common nuisance plants, and their berries often contaminate agricultural commodities. Black nightshade plants and their fruits contain solanaceous glycoalkaloids, but little information is available regarding their toxicity in vivo. Male and female rats were fed diets containing 0, 1, 5 or 25% (w/w) eastern black nightshade berries (BNB) for 13 weeks. BNB had no effect upon clinical appearance and behavior, body weight, food and water consumption, serum chemical profiles or organ weights. Gross or microscopic lesions related to BNB were not found. Anemia was present in high‐dose males after six weeks and in mid‐dose males, high‐dose males and high‐dose females after 13 weeks. Erythrocyte counts, hemoglobin concentrations and hematocrits of these groups were significantly decreased and averaged 81–93% of their respective control values. Erythrocyte counts, hemoglobin concentration and hematocrits of males fed 1% BNB, females fed 1% BNB and females fed 5% BNB averaged 94–97% of the control values after 13 weeks. These findings indicate that ingestion of low to moderate amounts of S. ptycanthum berries does not pose a significant health risk, although anemia may be a potential consequence of prolonged exposure to highly contaminated foodstuffs.

The effects of an interferon inducer, polyriboinosinic polyribocytidylic acid on cytochrome P-450 dependent hepatic progesterone metabolism

A time course study on the effects of an interferon inducing agent, polyriboinosinic polyribocytidylic acid (poly rIrC) on the hepatic cytochrome P-450 dependent progesterone metabolism was performed. Administration of a single dose of poly rIrC (10 mg/kg i.p.) to adult male Wistar rats caused a time dependent effect on liver weight, microsomal protein and total cytochrome P-450 levels, as well as the 16α and 6β hydroxylation of progesterone. The response was multiphasic, with a maximal depression of both hydroxylase activity 48 hours post-injection, followed by enhanced activity at 72 hours and subsequent return to control activity twenty-four hours later. A second less dramatic rise in the activities followed, bringing the 16α and 6β hydroxylase activity to 159% and 141% of their respective control values by 336 hours, at which point of time, the trend appeared to be still on the rise. The enhanced activity at 72 hours was preceded by an increase in serum cortisol and corticosterone levels, the ability of which to enhance the activity of 6β hydroxylation of steroids may partly explain the phenomenon.

Phenylephrine does not limit myocardial blood flow or oxygen delivery during isoflurane-induced hypotension in dogs.

Experiments were performed on seven fentanyl-pentobarbital-anesthetized, open-chest dogs to determine whether stimulation of coronary alpha 1-adrenergic receptors by phenylephrine causes coronary vasoconstriction and impaired myocardial oxygen delivery when phenylephrine is infused to correct isoflurane-induced hypotension. Myocardial blood flow was measured with radioactive microspheres, and myocardial oxygen and lactate extraction were determined. The Fick equation was used to calculate myocardial oxygen consumption. Measurements were obtained (a) under control conditions, (b) after a 30-min inhalation of isoflurane sufficient to decrease mean aortic pressure by 30%, and (c) while maintaining administration of isoflurane, 5-10 min after restoration of mean aortic pressure by intravenous infusion of phenylephrine. Isoflurane-induced hypotension was accompanied by a baroreceptor-mediated increase in heart rate and by a decrease in myocardial oxygen consumption; however, myocardial blood flow was maintained, resulting in decreased oxygen extraction and increased coronary sinus PO2, thus implying a direct coronary vasodilating effect for isoflurane. Lactate extraction was unaffected. Phenylephrine infusion during inhalation of isoflurane returned mean aortic pressure and heart rate to their respective control values, and it did not change myocardial oxygen consumption, myocardial blood flow, myocardial oxygen extraction, coronary sinus PO2, or lactate extraction from values obtained during isoflurane alone. These latter findings are consistent with undiminished coronary vasodilation by isoflurane in the presence of phenylephrine. In conclusion, infused phenylephrine to restore aortic pressure during isoflurane administration had no vasoconstrictor effect in the coronary circulation and did not impair myocardial oxygen delivery. Apparently, the direct coronary vasodilating action of isoflurane completely nullified phenylephrine-induced vasoconstriction via local alpha 1-adrenergic receptors.

Alteration of bile acid metabolism in two-thirds hepatectomized rat.

Bile acid metabolism after two-thirds partial hepatectomy (PH) in rat was studied. Bile acid kinetics (i.e. synthesis rate and pool size) were determined by wash out method combined with gas liquid chromatography, and serum bile acids by gas liquid chromatography-mass spectrometry. Serum bile acid concentration was highest on the third day after PH, as the liver regeneration progressed but it gradually decreased with increasing cholic acid (CA)/chenodeoxycholic acid (CDCA), reflecting impaired hepatic uptake of bile acids and/or cholestasis during the early post-hepatectomy period. Predominance of CA in bile acid synthesis, pool, and biliary secretion was also found. On the third day after PH, liver weight recovered to 66% of the control value, but enhancement of bile acid synthesis was not observed. Consequently, pool size remained at 50% of control. On the seventh day, synthesis of bile acid, especially of CA, was enhanced and pool size and liver weight returned to 68 and 72% of the respective control values. Bile acid synthesis was returned to the control value on the fourteenth day with concomitant restoration of liver weight and bile acid pool size. These changes in bile acid kinetics parallel the events during hepatic regeneration after PH.

Decrease in plasma GLP-1 immunoreactivity in starved rats

To determine whether starvation affects the metabolism of glucagon-like peptide-1 (GLP-1), we measured the plasma levels of proglucagon-derived peptides and the biosynthesis and posttranslational processing of proglucagon in groups of six rats starved for 1, 3 and 5 days. The plasma levels of GLP-1 immunoreactivity (GLP-1 IR) and glucagon-like immunoreactivity (GLI) decreased during starvation reaching 79 and 56% of the respective control values by day 5 ( P < 0.05 and < 0.01 vs control). The same is true of the plasma IRI level. The ileal contents of GLP-1 IR and GLI were 50.8 ± 3.8 pmol/g wet weight and 161.8 ± 13.2 pmol/g wet weight, respectively, on day 5 of starvation, which were significantly lower ( P < 0.01) than the respective values of 94.8 ± 16.6 pmol/g wet weight and 262.7 ± 28.1 pmol/g wet weight in control rats. However, the pancreatic contents of proglucagon-derived peptides tended to increase during starvation, although their increases were not statistically significant. No significant change in the posttranslational processing of proglucagon was detected during starvation. The decrease in the ileal proglucagon-derived peptides content was not associated with a decrease in intestinal proglucagon mRNA transcripts. These results suggested that decreased synthesis of proglucagon-derived peptides by the intestine was largely responsible for the reductions in their circulating levels in starved rats.

Role of nitric oxide in local blood flow control in the anaesthetized dog.

Intravenous infusion of NG-nitro-L-arginine methyl ester (L-NAME), a potent inhibitor of nitric oxide (NO) formation from L-arginine, provokes marked rises in arterial blood pressure by increasing peripheral resistance. In order to further evaluate the contribution of basal NO-formation to control of organ blood flow, regional blood flow distribution within the myocardium, kidney and brain areas was assessed using the tracer-microsphere technique in anaesthetized dogs. After L-NAME (20 mg kg-1 i.v.) kidney perfusion was homogeneously reduced by 55% in the entire cortex and the outer medulla. Within the left ventricular myocardium regional blood flow significantly decreased only in subepicardial layers (-12%), whereas within the entire right ventricle regional blood flow was reduced by 19-24%. A close inverse relationship was found between all changes in regional myocardial blood flows observed after L-NAME and the respective control values. No significant changes in regional blood flow in different areas of the brain were detectable after L-NAME. It is concluded that the contribution of basal NO formation varies greatly between different organs and exhibits significant regional differences within the heart. It is possible that local metabolic mechanisms may compensate functionally for the inhibition of NO synthesis.

Vegetarians have higher plasma alpha-tocopherol relative to cholesterol than do nonvegetarians.

Biological antioxidants are thought to play a protective role in certain disease processes, including atherosclerosis. To compare the relative antioxidant/atherogenic risk between vegetarians (presumed lower risk) and omnivores (higher risk), the alpha-tocopherol, total cholesterol and fatty acid (FA) profiles were determined in the plasma of 79 vegetarians (28 males, 51 females) and 79 age- and sex-matched nonvegetarians. In the vegetarian group, mean (+/- SEM) plasma alpha-tocopherol was 714 +/- 46 micrograms/dl for males and 725 +/- 24 for females; corresponding cholesterol values were 122 +/- 5 mg/dl and 138 +/- 3, respectively, which were significantly lower than the respective control values (928 +/- 38; 883 +/- 23 and 206 +/- 6; 188 +/- 4). However, when plasma tocopherol was expressed in terms of cholesterol, the tocopherol: cholesterol molar ratio was significantly enhanced for both male (27%) and female (11%) vegetarians. Vegetarians also had a lower atherosclerosis risk based on their plasma FA profile (higher linoleic:oleic acid ratio) which correlated well (r = 0.72; p less than 0.001) with plasma alpha-tocopherol:cholesterol molar ratio. Since the bulk of tocopherol is transported in low-density lipoprotein, this lipoprotein in vegetarians may be better protected against lipid peroxidation, a process believed to be important in the pathogenesis of atherosclerosis.

Effects of triiodothyronine in spontaneously hypertensive rats. Studies on cardiac metabolism, function, and heart weight.

We have studied the effects of triiodothyronine (T3) on heart function, on the myocardial oxidative pentose phosphate pathway, and on heart weight in spontaneously hypertensive (SHR) rats. Another aim was to examine whether these T3-effects may be reversible. T3 was administered daily (0.2 mg/kg s.c.) for 14 days. Compared to the untreated SHR controls, T3 induced an increase in heart rate (beats/min) from 357 +/- 10 (n = 17) to 553 +/- 10 (n = 17), in the pressure-rate-product (mm Hg/min) from 78 400 +/- 4500 (n = 15) to 113 700 +/- 4800 (n = 15), and in the heart weight/body weight ratio (mg/g) from 4.2 +/- 0.2 (n = 20) to 5.8 +/- 0.2 (n = 19). The activity of myocardial glucose-6-phosphate dehydrogenase, the first and rate-limiting enzyme of the oxidative pentose phosphate pathway (units/g protein), was elevated from 4.2 +/- 0.2 (n = 9) to 7.0 +/- 0.6 (n = 9) after 14 days of T3-treatment, while the activity of 6-phosphogluconate dehydrogenase, one of the following enzymes in the pathway, was not altered appreciably. These changes returned to the respective control values when T3-treatment was discontinued for 14 days. Our results demonstrate that T3 had a positive chronotropic effect and induced an additional heart enlargement in an animal model with already established cardiac hyperfunction and hypertrophy. The effects on heart function and weight, which were fully reversible, were not as pronounced as in normal Sprague-Dawley rats.

In vitro and in vivo studies of the effect of vitamin E on microsomal cytochrome P450 in rat liver

Administration of a diet supplemented with 0.06% vitamin E acetate to male rats over a 6-week period doubled hepatic microsomal stores of α-tocopherol over those in control (vitamin E adequate) rat liver. Total cytochrome P450 content and NADPH-cytochrome P450 reductase activity were significantly elevated in hepatic microsomes from vitamin E-supplemented rats to 111% and 123% of respective control values. Androstenedione 16α-hydroxylase activity was increased in these fractions (2.57 ± 0.31 nmol product/min/mg protein vs 1.81 ± 0.38 in controls) whereas activities of the 6β-, 7α- and 16β-hydroxylase pathways were unchanged. Immunoquantitation of the microsomal 16α-hydroxylase, P450 IIC11, indicated a corresponding increase in the hepatic content of the enzyme. In view of the established antioxidant role of tocopherols, the effects of dietary vitamin E manipulation on the concentration of protein sulphydryl groups and the susceptibility of microsomes to ferric sulphate-ADP-NADPH-mediated lipid peroxidation were also assessed. Dietary supplementation did not influence microsomal protein sulphydryl content (68 ± 10 nmol glutathione equivalents/mg protein) but decreased the extent of lipid peroxidation produced by the ferric sulphate-ADP-NADPH system in vitro. Further in vitro experiments demonstrated that vitamin E acetate (2 μM) protected protein sulphydryl groups and lipids against peroxidation in control microsomes and partially reduced the associated losses of P450-mediated steroid hydroxylase activities. Western immunoquantitation of P450 IIC11 revealed that exogenous vitamin E acetate protected completely against peroxidation-induced apoprotein loss. These studies establish that the in vitro protective effects of vitamin E acetate against sulphydryl and lipid peroxidation extend to protection of the P450 apoprotein but that enzyme activity is only partially protected. This finding suggests that peroxidation-dependent loss of P450 in vitro is mediated by haem degradation from the P450 holoenzyme and is not directly related to lipid/sulphydryl oxidation. In contrast, the in vivo effects of dietary vitamin E on drug metabolizing enzymes are regulatory in nature and are unrelated to effects on lipid peroxidation.

Corticotropin response to combined administration of human corticotropin-releasing hormone and small-dose arginine vasopressin in normal subjects

Arginine vasopressin (AVP) is known to potentiate corticotropin (ACTH) secretion by human corticotropin-releasing hormone (hCRH), and a combined administration of hCRH and AVP appears useful as a pituitary ACTH reserve test. This study was designed to evaluate the appropriate dose of AVP and its route of administration for better estimation of pituitary ACTH reserve in humans, when used in combination with a conventional hCRH stimulation test. First, intravenous (IV) doses of hCRH (100 μg) and AVP (0, 0.1, and 0.3 U) were administered simultaneously in six normal subjects. Second, IV hCRH was administered with intramuscular (IM) AVP (0, 1.0, 3.0, and 5.0 U) in 10 normal subjects. Blood samples for measurement of plasma ACTH were obtained at 0, 15, 30, 45, 60, 90, and 120 minutes after the hCRH with and without AVP administration. The order of AVP doses was randomly chosen in each subject. The peak plasma ACTH level was 65.0 ± 16.0 pg/mL (30 minutes) with hCRH alone and 139.5 ± 35.6 pg/mL (15 minutes) with hCRH plus 0.3 U IV AVP in six normal subjects. Similarly, the peak plasma ACTH level was 43.5 ± 5.6 pg/mL (30 minutes) with hCRH alone and 116.0 ± 19.6 (15 minutes) and 96.6 ± 24.0 pg/mL (15 minutes) with hCRH plus 3.0 and 5.0 U IM AVP in 10 normal subjects, respectively. The hCRH-induced ACTH responses (Δ ACTH) with both IV and IM AVP were significantly ( P < .05) greater than the respective control values with hCRH alone. The responses (Δ ACTH) were comparable between the two phases of 3.0 and 5.0 U IM AVP. Two subjects complained of facial flushing with 5.0 U IM AVP, whereas the tests with hCRH plus 3.0 U IV AVP and 3.0 U IM AVP were well tolerated in all subjects. The results suggest that the simultaneous administration of hCRH (100 μg) with IV AVP (0.3 U) or with IM AVP (3.0 U) is useful and safe method for evaluating the pituitary ACTH reserve in humans. The clinical significance of the test in pituitary-adrenal disorders remains to be seen in future studies.

Cerebral oxidative metabolism and redox state during hypoxia-ischemia and early recovery in immature rats

Intracellular pH (pHi) and cytoplasmic and mitochondrial oxidation-reduction (redox) states of cerebral tissue were examined in relation to perturbations of glycolytic and tricarboxylic acid cycle intermediates and of high-energy phosphate reserves during hypoxia-ischemia and the early recovery period in the immature rat. Seven-day postnatal rats underwent unilateral common carotid artery ligation and exposure to 8% O2 for 3 h, after which they were quick frozen in liquid N2 at the terminus of hypoxia-ischemia and at 10, 30, 60, and 240 min of recovery for enzymatic fluorometric analysis of cerebral metabolites. During hypoxia-ischemia, concentrations of glucose and alpha-ketoglutarate in the cerebral hemisphere ipsilateral to the carotid artery occlusion were depleted to 10 and 70% of control, respectively; pyruvate was unchanged. During recovery, glucose, pyruvate, and alpha-ketoglutarate increased above their respective control values. Calculated pHi decreased from 7.0 (control) to 6.6 during hypoxia-ischemia and normalized by 10 min of recovery. The cytoplasmic NAD+/NADH ratio decreased (increased reduction) to 50% of control during hypoxia-ischemia and remained in the reduced state throughout 4 h of recovery. Paradoxically, mitochondrial NAD+/NADH was oxidized at the terminus of hypoxia-ischemia. The mitochondrial oxidation which developed during hypoxia-ischemia presumably results from a limitation of cellular substrate (glucose) supply, which in turn leads to a depletion of high-energy phosphate reserves, culminating in brain damage.

Single- versus dual-chamber sensor-driven pacing: Comparison of cardiac outputs

Previous studies have shown that single-chamber sensor-driven pacing improves exercise tolerance for patients with chronotropic incompetence. However, long-term single-chamber pacing has a number of inherent problems that limit its usefulness. Although sensor-driven dual-chamber pacing largely obviates the problems inherent with single-chamber sensor-driven pacing, the physiologic benefit of dual-chamber sensor-driven pacing has not yet been demonstrated. Accordingly, the purpose of this study was to compare exercise-induced cardiac output for patients with chronotropic incompetence, after programming their pacemakers to either a simulated sensor-driven single or simulated dual-chamber mode. Cardiac output was measured noninvasively at rest and peak exercise using standard Doppler-derived measurements, obtained in a blinded fashion. At rest the Doppler-derived resting VVI and DDD cardiac outputs were 4.49 ± 0.3 L/min and 4.68 ± 0.3 L/min, respectively. At peak exercise, the DDD cardiac output was 5.07 ± 0.5 L/min, whereas the simulated activity VVI and DDD cardiac outputs were 6.33 ± 0.6 L/min and 7.41 ± 0.70 L/min, respectively. Analysis of variance showed that there was an overall significant difference in cardiac output from rest to peak exercise ( p < 0.001). However, only the simulated activity DDD cardiac output was significantly different from its respective control value ( p < 0.05). Thus this study shows for the first time that the addition of rate responsiveness to dual-chamber pacing results in a significant improvement in cardiac output for patients with chronotropic incompetence.

Effect of BN 50739, a new platelet activating factor antagonist, on ischaemia induced ventricular arrhythmias in isolated working rat hearts

The aim was to investigate the role of platelet activating factor (PAF) in myocardial ischaemia by using BN 50739, a new specific PAF receptor antagonist with a hetrazepine framework. Isolated working rat hearts were subjected to regional ischaemia, induced by ligation of the left main coronary artery for 30 min, followed by reperfusion. BN 50739 was applied at concentrations of 10(-7), 10(-6), 10(-5) and 5 X 10(-5) M, and its effects on the incidence of ischaemia induced and reperfusion induced ventricular tachycardia and ventricular fibrillation and heart functions, such as heart rate, coronary flow, aortic flow, left ventricular developed pressure (LVDP), its first derivative (LVdP/dtmax), and left ventricular end diastolic pressure (LVEDP), were determined. Studies were performed on isolated working hearts of male Sprague-Dawley rats weighing 300-360 g. Hearts were perfused with BN 50739 dissolved in dimethylsulphoxide. Control hearts were perfused with the vehicle. Regional ischaemia triggered ventricular arrhythmias showing high incidence between 12 and 20 min with peak appearance at 16 min. BN 50739 induced dose dependent protection against ventricular tachycardia and fibrillation: incidences declined from their respective control values of 91% and 75% to 33% (p less than 0.05) and 8% (p less than 0.05) after exposure to 10(-5) M, and to 25% (p less than 0.05) and 8% (p less than 0.05) after exposure to 5 X 10(-5) M concentrations. Reperfusion of the ischaemic myocardium resulted in an immediate appearance of ventricular tachycardia and fibrillation, but these were not suppressed by the PAF antagonist. Regional ischaemia slightly reduced heart rate, markedly decreased coronary flow, aortic flow, LVDP and LVdP/dtmax, and increased LVEDP. With the exception of LVEDP, these variables were not influenced by the drug. BN 50739, applied at a concentration of 5 X 10(-5) M, reduced LVEDP significantly during the whole ischaemic period. Under in vitro conditions PAF is likely to be involved in the genesis of ischaemia induced ventricular arrhythmias since BN 50739, a specific PAF receptor antagonist, exerts a protective effect against these rhythm disturbances. This suggests that PAF antagonists may have benefit in the clinical management of acute myocardial ischaemia.

Effect of glucose and insulin on triacylglycerol metabolism in isolated normal and diabetic skeletal muscle

The effects of insulin and glucose on triacylglycerol (TG) metabolism in normal and diabetic isolated skeletal muscle were investigated in this study. Intracellular TG was continuously synthesized and hydrolyzed in both normal and diabetic skeletal muscle. In the absence of insulin and glucose, normal and diabetic skeletal muscle TG content and synthesis were decreased. In contrast, in the presence of insulin and glucose, the normal and diabetic TG contents were unchanged and triacylglycerol synthesis was increased as compared with the respective control values. However, insulin and glucose increased intramuscular TG content to a greater extent than could be accounted for by their stimulation of TG synthesis, indicating that insulin and glucose appear to inhibit TG hydrolysis in diabetic muscle, as well as in normal muscle. In addition, these data suggest that diabetes causes a defect in the ability of insulin and glucose to stimulate TG synthesis, as the increase in diabetic muscle TG synthesis in the presence of insulin and glucose was less than in normal muscle.

Induction of Na(+)-K(+)-ATPase subunit mRNAs by cycloheximide in a rat liver cell line

Exposure of confluent Clone 9 cells to 40 microM cycloheximide (CHX), a concentration sufficient to inhibit leucine incorporation by 95% within 5 min, coordinately increased the abundances of Na(+)-K(+)-ATPase subunit mRNAs, mRNA alpha 1 and mRNA beta 1. The CHX-induced increases in mRNA alpha 1 and mRNA beta 1 abundances were, respectively, 1.8- and 1.9-fold at 40 min and 3.0- and 3.3-fold at 6 h. Augmented subunit mRNA contents were also observed after exposure to other protein synthesis inhibitors including 100 microM anisomycin and 100 microM emetine. Upon removal of CHX, the rate of leucine incorporation returned to control values within 1 h, but mRNA alpha 1 and mRNA beta 1 content decreased only slowly and were still elevated at 24 h at 1.7- and 1.8-fold the respective control values. Despite the persistence of increased levels of the subunit mRNAs and normalization of the rate of leucine incorporation, Na(+)-K(+)-ATPase activity was unchanged at 3, 6, 24, and 48 h after removal of CHX. In cells "depleted" of protein kinase C (PKC) activity after a 24-h preincubation in the presence of 160 nM 12-O-tetradecanoylphorbol-13-acetate (TPA), mRNA alpha 1 and mRNA beta 1 abundances were still inducible by CHX. It is concluded that exposure of Clone 9 cells to CHX and other inhibitors of protein synthesis results in increased abundances of Na(+)-K(+)-ATPase subunit mRNAs independently of PKC activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Relative Cataractogenic Effects of X Rays, Fission-Spectrum Neutrons, and 56 Fe Particles: A Comparison with Mitotic Effects

The eyes of Sprague-Dawley rats were irradiated with doses of 2.5-10 Gy 250-kVp X rays, 1.25-2.25 Gy fission-spectrum neutrons (approximately 0.85 MeV), or 0.1-2.0 Gy 600-MeV/A 56Fe particles. Lens opacifications were evaluated for 51-61 weeks following X and neutron irradiations and for 87 weeks following X and 56Fe-particle irradiations. Average stage of opacification was determined relative to time after irradiation, and the time required for 50% of the irradiated lenses to achieve various stages (T50) was determined as a function of radiation dose. Data from two experiments were combined in dose-effect curves as T50 experimental values taken as percentages of the respective T50 control values (T50-% control). Simple exponential curves best describe dose responsiveness for both high-LET radiations. For X rays, a shallow dose-effect relationship (shoulder) up to 4.5 Gy was followed at higher doses by a steeper exponential dose-effect relationship. As a consequence, RBE values for the high-LET radiations are dose dependent. Dose-effect curves for cataracts were compared to those for mitotic abnormalities observed when quiescent lens epithelial cells were stimulated mechanically to proliferate at various intervals after irradiation. Neutrons were about 1.6-1.8 times more effective than 56Fe particles for inducing both cataracts and mitotic abnormalities. For stage 1 and 2 cataracts, the X-ray Dq was 10-fold greater and the D0 was similar to those for mitotic abnormalities initially expressed after irradiation.

Brown adipose tissue thermogenic responses of rats induced by central stimulation: effect of age and cold acclimation.

1. Urethane-anaesthetized, age-matched cold-(4 degrees C) and room (21 degrees C)-acclimated groups of Sprague-Dawley rats were given repeated (three) ventromedial hypothalamic electrical stimulations. Interscapular brown adipose tissue (IBAT), colonic, surface tail temperatures and blood pressure were monitored before and after each electrical stimulation. Propranolol HCl (2.5 mg kg-1 i.v.) was given 10 min prior to the last (third) ventromedial hypothalamic stimulation. 2. Repeated electrical stimulation of the ventromedial hypothalamic (VMH) nucleus to either small or large rats (kept at 21 degrees C) caused no significant change in interscapular brown fat, colonic or surface temperatures compared to respective pre-stimulation control values whereas mean arterial pressure was slightly but significantly increased during the 30 s stimulation period. 3. Electrical stimulation of the ventromedial hypothalamic nucleus of small or large rats, kept at 4 degrees C for 3 weeks prior to testing, caused significant (greater than 0.25 and greater than 0.40 degrees C, respectively) rises in interscapular BAT temperature from respective prestimulation control values. Colonic temperatures increased following ventromedial hypothalamic electrical stimulation only in the small, 4 degrees C-acclimated group whereas surface tail temperatures did not significantly change after stimulation of either cold-exposed group. Mean arterial pressures were significantly increased during ventromedial hypothalamic electrical stimulation in both 4 degrees C-acclimated groups, compared to pre-stimulation control levels and, in addition, were above those of age-matched rats kept at 21 degrees C. Intravenous propranolol, which decreased interscapular brown fat and colonic temperatures in all groups, blocked the rise in interscapular brown fat and colonic temperatures of the 4 degrees C-acclimated rats following the last electrical stimulation of the ventromedial hypothalamic nucleus. 4. In vitro biochemical analysis of the interscapular brown fat pads of another four groups of age-matched, small and large 21 and 4 degrees C-acclimated rats revealed that the thermogenic capacity of the 4 degrees C-acclimated groups was, in all cases, significantly increased from age-matched groups previously kept at 21 degrees C, as shown by significant increases in brown adipose tissue mass, BAT DNA and protein content, BAT mitochondrial protein and BAT mitochondrial GDP binding.(ABSTRACT TRUNCATED AT 400 WORDS)