We investigated the lipolytic effect of several hormones on isolated human adipocytes obtained at different donor ages. In neonates, noradrenaline and adrenaline had an insignificant lipolytic effect (70% over basal). In this age group only thyrotropin (TSH) had a significant effect in physiological concentrations, and the maximal lipolytic effect (700% over basal) was the same as that of isoprenaline. The lipolytic effect of TSH was the same in premature 4-10-wk-old infants with a gestational age of 27-33 wk as in neonates, but fat cells from infants 4-10 wk old, born at term, showed a significantly lower effect. In children and adults, the lipolytic effect of TSH gradually decreased further and was present only in unphysiological concentrations. The catecholamine-induced lipolysis was pronounced and was similar in children and adults (350% over basal). TSH is the dominating lipolytic hormone in vitro during the neonatal period. Thus, the peak elevation of circulating TSH, which is seen immediately after birth, may be essential to lipolysis during this part of life.

OBJECTIVE

beta(1) and beta(2)-adrenoceptors coexist in murine heart but beta(2)-adrenoceptor-mediated effects have not been detected in atrial and ventricular tissues, possibly due to marked phosphodiesterase (PDE) activity. We investigated the influence of the PDE3 inhibitor cilostamide and PDE4 inhibitor rolipram on the effects of (-)-adrenaline in three regions of murine heart.

METHODS

(-)-Adrenaline-evoked cardiostimulation was compared on sinoatrial beating rate, left atrial and right ventricular contractile force in isolated tissues from 129SvxC57B1/6 cross mice. Ventricular arrhythmic contractions were also assessed.

RESULTS

Both rolipram (1 microM) and cilostamide (300 nM) caused transient sinoatrial tachycardia but neither enhanced the chronotropic potency of (-)-adrenaline. Rolipram potentiated 19-fold (left atrium) and 7-fold (right ventricle) the inotropic effects of (-)-adrenaline. (-)-Adrenaline elicited concentration-dependent ventricular arrhythmias that were potentiated by rolipram. All effects of (-)-adrenaline were antagonized by the beta(1)-adrenoceptor-selective antagonist CGP20712A (300 nM). Cilostamide (300 nM) did not increase the chronotropic and inotropic potencies of (-)-adrenaline, but administered jointly with rolipram in the presence of CGP20712A, uncovered left atrial inotropic effects of (-)-adrenaline that were prevented by the beta(2)-adrenoceptor-selective antagonist ICI118551.

CONCLUSIONS

PDE4 blunts the beta(1)-adrenoceptor-mediated effects of (-)-adrenaline in left atrium and right ventricle but not in sinoatrial node. Both PDE3 and PDE4 reduce basal sinoatrial rate in a compartment distinct from the beta(1)-adrenoceptor compartment. PDE3 and PDE4, acting in concert, prevent left atrial beta(2)-adrenoceptor-mediated inotropy. PDE4 partially protects the right ventricle against (-)-adrenaline-evoked arrhythmias.

Two deaths after sudden severe asthma attacks in young people are reported from a clinic set up to identify and manage "at risk" patients. These deaths occurred despite frequent visits at which recommendations made by previous studies were implemented. The risk factors and management of such episodes have been reviewed. Precautions taken proved inadequate due to the severe, abrupt nature of the attacks, failure of the patients' immediate treatment, and delay in reaching hospital. Consideration should be given to the self-administration of subcutaneous adrenaline or specific beta-agonists, the provision of a detailed medical card, and free access to the nearest hospital in such cases.

1. Human platelet-rich plasma prelabelled with [(3)H]adenine was incubated at 37 degrees C with antimycin A and 2-deoxy-d-glucose. Variations in the amounts of ATP, ADP and P(i), and in the radioactivity of ATP, ADP, AMP, IMP, hypoxanthine+inosine and adenine were determined during incubation. Adrenaline- and ADP-induced platelet aggregation and the ADP-induced shape change of the platelets were determined concurrently. 2. 2-Deoxyglucose caused conversion of [(3)H]ATP to [(3)H]hypoxanthine+inosine. The rate of this conversion increased with increasing 2-deoxyglucose concentration and was markedly stimulated by addition of antimycin, which had no effect alone. At maximal ATP-hypoxanthine conversion rates, the IMP radioactivity remained at values tenfold higher than control, whereas [(3)H]ADP and [(3)H]AMP radioactivity gave variations typical for product/substrates in consecutive reactions. The specific radioactivityof ethanol-soluble platelet ATP decreased during incubation to less than one-tenth of its original value. The amounts and radioactivity of ethanol-insoluble ADP did not vary during incubation with the metabolic inhibitors. 3. The rate of ADP- and adrenaline-induced primary aggregation decreased as the amount of radioactive ATP declined, and complete inhibition of aggregation was obtained at a certain ATP concentration (metabolic ATP threshold). This threshold decreased with increasing concentration of inducer ADP. 4. Secondary platelet aggregation (release reaction) had a metabolic ATP threshold markedly higher than that of primary aggregation. 5. Shape change was gradually inhibited as the ATP radioactivity decreased, and had a metabolic ATP threshold distinctly lower than that of primary aggregation, and which decreased with increasing concentration of ADP. 6. A small but distinct fraction of [(3)H]ATP disappeared rapidly during the combined shape change-aggregation process induced by ADP in platelets incubated with metabolic inhibitors, whereas no ATP disappearance occurred during aggregation in their absence.

Opioid involvement in the physiological and hormonal responses to acute exercise was investigated in six normal male subjects. Each was exercised to 40% (mild exercise) and 80% (severe exercise) of his previously determined maximal oxygen consumption on two occasions, with and without an infusion of high-dose naloxone. The exercise task was a bicycle ergometer; mild and severe exercise were performed for 20 min each, followed by a recovery period. Exercise produced the expected increases in heart rate, blood pressure, ventilation, tidal volume, respiratory rate, oxygen consumption and carbon dioxide production. After severe exercise, naloxone infusion increased ventilation from 94.8 +/- 4.9 litres/min to 105.7 +/- 5.0 litres/min (P less than 0.05), but had no effect on any of the other physiological variables. Exercise-induced changes in several hormones and metabolites were noted, including elevations in circulating lactate, growth hormone (GH), prolactin, cortisol, luteinizing hormone (LH), follicle stimulating hormone (FSH), adrenaline noradrenaline, plasma renin activity (PRA) and aldosterone. There was no change in plasma met-enkephalin. Naloxone infusion produced the expected increases in LH and cortisol, but also significantly enhanced the elevations in prolactin, adrenaline, noradrenaline, plasma renin activity and aldosterone (P less than 0.05). Psychological questionnaires revealed minor mood changes after exercise, but no evidence was found for the suggested 'high' or euphoria of exercise. Effort was perceived as greater during the naloxone infusion than the saline infusion in every subject.(ABSTRACT TRUNCATED AT 250 WORDS)

Breakdown of short-term fractal-like behaviour of HR indicates an increased risk for adverse cardiovascular events and mortality, but the pathophysiological background for altered fractal HR dynamics is not known. Our aim was to study the effects of pharmacological modulation of autonomic function on fractal correlation properties of heart rate (HR) variability in healthy subjects. Short-term fractal scaling exponent (alpha1) along with spectral components of HR variability were analysed during the following pharmacological interventions in healthy subjects: (i) noradrenaline (NE) infusion (n=22), (ii) NE infusion after phentolamine (PHE) (n=8), (iii) combined NE + adrenaline (EPI) infusion (n=12), (iv) vagal blockade with high dose of atropine (n=10), (v) and vagal activation by low dose of atropine (n=10). Then alpha1 decreased progressively during the incremental doses of NE (from 0.85 +/- 0.250 to 0.55 +/- 0.23, P<0.0001). NE also decreased the average HR (P<0.001) and increased the high frequency spectral power (P<0.001). Vagal blockade with atropine increased the alpha1 value (from 0.82 +/- 0.22 to 1.24 +/- 0.41, P<0.05). Combined NE + EPI infusion and vagal activation with a low dose atropine did not result in any changes in alpha1, and alpha-adrenergic blockade by PHE did not completely reverse the effects of NE on alpha1. Increased levels of circulating NE result in reduction of short-term correlation properties of HR dynamics. The results suggest that coactivation of cardiac vagal outflow at the time of high levels of a circulating sympathetic transmitter explains the breakdown of fractal-like behaviour of human HR dynamics.

The biochemical and clinical response to massage in preterm infants was assessed. Eleven stable infants, of 29 weeks' median gestational age, median birth weight 980 g, and median postnatal age 20 days, were studied. Blood samples were obtained for the determination of adrenaline, noradrenaline, and cortisol 45 minutes before the start of massage and approximately one hour after completion of massage. Cortisol, but not catecholamine, concentrations decreased consistently after massage (median difference -35.8 nmol/l; 95% confidence interval -0.5 to -94.0, Wilcoxon matched pairs). There was a slight decrease in skin temperature (median difference -0.36 degrees C, 95% confidence interval -0.09 to -0.65) but there was no change in oxygenation or oxygen requirement. This study has shown that it is possible to detect an objective hormonal change following a supposedly 'non-therapeutic' intervention in preterm infants. The development of such methods of assessment are likely to be of particular relevance in the extremely immature or ill neonate in whom behavioural evaluation cannot play more than a limited part.

Male and female university students were exposed to two different stressors in each of two 110-min sessions, i.e., a cognitive task (color-word conflict) and repeated venipuncture. Catecholamine excretion, heart rate, and subjective reactions were measured. Control values were obtained under conditions of relaxation in the laboratory. Subjects of both sexes responded to both stressors by increased heart rate and feelings of unpleasantness and distress. The pattern of adrenaline excretion, however, differed between sexes: in males both stressors induced a significant increase, whereas in females adrenaline excretion remained on the same level under the two stress conditions as during relaxation; Noradrenaline excretion was not systematically affected by either stressor in either sex group.

In isolated electrically driven right auricular strips of human hearts (1 Hz at 37 degrees C) the ability of the endogenous catecholamines noradrenaline, adrenaline, and dopamine to mediate positive inotropic effects by stimulation of myocardial alpha-adrenoceptors was investigated. 1. The concentration-response curve for the positive inotropic effect of noradrenaline was shifted to the right by pindolol, 10(-8)M, whereas the additional blockade by phentolamine, 3 x 10(-6)M, was without further effect; therefore, the positive inotropic effect of noradrenaline is mediated by beta-adrenoceptors only. 2. In contrast, the positive inotropic effects of adrenaline as well as of dopamine are caused by stimulation of both, beta- and alpha-adrenoceptors. 3. These results are discussed with respect to the possible physiological and pathophysiological function of myocardial alpha-adrenoceptors.

A wealth of studies performed with a spectrum of methods spanning simple clearance studies to the molecular identification of ion transporters has increased our understanding of how approximately 1.7 kg of NaCl and 180 L of H2O are absorbed by renal tubules in man and how the urinary excretion is fine-tuned to meet homeostatic requirements. This review will summarize our current understanding. In the proximal nephron, approximately 60 to 70% of the filtered Na+ and H2O is absorbed together with approximately 90% of the filtered HCO3-. The exact quantities are determined by many regulatory factors, such as glomerulotubular balance, angiotensin II, endothelin, sympathetic innervation, parathyroid hormone, dopamine, acid base status and others. The essential components of absorption are luminal membrane Na+/H+ exchange and the basolateral (Na+ + K+)-ATPase. In the thick ascending limb of the loop of Henle, 20 to 30% of the filtered NaCl is absorbed via Na+2Cl-K+ cotransport driven by the basolateral (Na+ + K+)-ATPase. No H2O is absorbed at this nephron site. The transport rate is determined by the Na+ load and by several hormones and neurotransmitters, including prostaglandins, parathyroid hormone, glucagon, calcitonin, arginine vasopressin (AVP), and adrenaline. In the distal tubule, some 5 to 10% of the filtered load is absorbed via Na+Cl- cotransport in the luminal membrane driven by the basolateral (Na+ + K+)-ATPase. The rate of transport is again determined by the delivered load and by several hormones and neurotransmitters. One of the tasks of the collecting duct is to control the absorption of approximately 10 to 15% of the filtered H2O, regulated by AVP, and just a few percent of the filtered Na+, controlled by aldosterone and natriuretic hormone. The water absorption proceeds through the luminal membrane via aquaporin 2 and through the basolateral membrane via aquaporin 3 channels and is driven by the osmotic gradient built up by the counter current concentrating system. The Na+ absorption occurs via Na+ channels present in the luminal membrane driven by the basolateral (Na+ + K+)-ATPase. With no pharmacological interference, urinary excretion of Na+ can vary between less than 0.1% and no more than 3% of the filtered load, and that of H2O can vary between 0.3 and 15%.

Increases in plasma noradrenaline (NA) concentration occur during moderate to heavy exercise in man. This study was undertaken to examine the spillover of NA from both resting and contracting skeletal muscle during exercise. Six male subjects performed one-legged knee-extension so that all measurements could be made both in the exercising and in the resting leg. Subjects exercised for 10 min at each of 50% and 100% of the peak performance capacity of the leg. Leg blood flow was measured by thermodilution and blood samples were drawn for the determination of plasma NA and adrenaline, first in the resting leg and then in the exercising leg. To calculate NA spillover, the extraction of NA (NAe) or of adrenalin (Ae) is required: NAe was measured by repeating the experiment under constant [3H]NA infusion following a 40-min rest period. During exercise, NA spillover was significantly larger in the exercising leg than in the resting leg both during 50% and 100% leg exercise. These results suggest that contracting skeletal muscle may contribute to a larger extent than resting skeletal muscle to increasing the level of plasma NA during exercise. Contractile activity may influence the NA spillover from skeletal muscle by a presynaptic and/or postsynaptic influence on the sympathetic nervous activity to this tissue.

Ghrelin is a novel GH (growth hormone)-releasing peptide isolated from the stomach. The cardiovascular and hormonal effects of the subcutaneous administration of ghrelin in humans remain unknown. Six healthy volunteers each received subcutaneous administration of three doses of ghrelin (1, 5 or 10 microg/kg) and placebo; the order of administration was randomized, and separate doses were given at least 24 h apart. The serum GH level dose-dependently increased from 0.5 +/- 0.4 to 3.6 +/- 2.1 ng/ml (1 microg/kg ghrelin; P=0.99 compared with baseline), 27.1 +/- 12.0 ng/ml (5 microg/kg; P<0.01 compared with baseline) and 45.4 +/- 12.8 ng/ml (10 microg/kg; P<0.01 compared with baseline) 30 min after ghrelin administration. Subcutaneous administration of ghrelin did not significantly alter circulating levels of corticotropin, cortisol, insulin-like growth factor-1, noradrenaline or adrenaline, although 10 microg/kg ghrelin slightly increased the prolactin level. No significant changes in heart rate or mean arterial pressure were observed. In contrast, the left ventricular ejection fraction, as assessed by echocardiography, increased dose-dependently from 63.5 +/- 0.6% to 65.1 +/- 0.9% (1 microg/kg ghrelin; P=0.97 compared with baseline), 69.6 +/- 1.3% (5 microg/kg; P<0.01 compared with baseline) and 71.5 +/- 0.9% (10 microg/kg; P<0.01 compared with baseline) 30 min after ghrelin administration. These haemodynamic and hormonal changes were still apparent 60 min after ghrelin injection. In conclusion, subcutaneous administration of ghrelin dose-dependently induced relatively specific GH release and enhanced cardiac performance in humans.

The responses to brief maximal exercise of 10 male subjects have been studied. During 30 s of exercise on a non-motorized treadmill, the mean power output (mean +/- SD) was 424.8 +/- 41.9 W, peak power 653.3 +/- 103.0 W and the distance covered was 167.3 +/- 9.7 m. In response to the exercise blood lactate concentrations increased from 0.60 +/- 0.26 to 13.46 +/- 1.71 mmol.l-1 (p less than 0.001) and blood glucose concentrations from 4.25 +/- 0.45 to 5.59 +/- 0.67 mmol.l-1 (p less than 0.001). The severe nature of the exercise is indicated by the fall in blood pH from 7.38 +/- 0.02 to 7.16 +/- 0.07 (p less than 0.001) and the estimated decrease in plasma volume of 11.5 +/- 3.4% (p less than 0.001). The plasma catecholamine concentrations increased from 2.2 +/- 0.6 to 13.4 +/- 6.4 nmol.l-1 (p less than 0.001) and 0.2 +/- 0.2 to 1.4 +/- 0.6 nmol.l-1 (p less than 0.001) for noradrenaline (NA) and adrenaline (AD) respectively. The plasma concentration of the opioid beta-endorphin increased in response to the exercise from less than 5.0 to 10.2 +/- 3.9 p mol.l-1. The post-exercise AD concentrations correlated with those for lactate as well as with changes in pH and the decrease in plasma volume. Post-exercise beta-endorphin levels correlated with the peak speed attained during the sprint and the subjects peak power to weight ratio. These results suggest that the increases in plasma adrenaline are related to those factors that reflect the stress of the exercise and the contribution of anaerobic metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

1. 3H-Noradrenaline was infused intravenously into pentobarbitone anaesthetized rabbits to reach a steady-state plasma 3H-noradrenaline level, from which the noradrenaline plasma clearance was calculated. The plasma level of endogenous noradrenaline was determined simultaneously and the rate of noradrenaline release was then derived. 2. Pargyline, amezinium, desipramine and guanethidine all reduced the noradrenaline plasma clearance. The noradrenaline release rate was decreased by desipramine, guanethidine and clonidine. 3. Adrenaline (6 nmol/kg i.v. twice) enhanced the noradrenaline release rate by 53%. This effect was apparent after the plasma adrenaline has returned to basal levels. The adrenaline levels in sympathetically innervated tissues were elevated at this time. 4. When the rabbits were pretreated with either propranolol HCl (1 mg/kg i.p.) to block beta-adrenoceptors, or desipramine HCl (1 mg/kg i.v.) to block neuronal uptake, the facilitatory effect of adrenaline was abolished. Noradrenaline (6 nmol/kg i.v. twice) had no effect on the noradrenaline release rate. 5. These findings suggest that if the sympathetic transmitter stores contain sufficient adrenaline neuronally released adrenaline may modulate noradrenaline release in vivo by activating facilitatory presynaptic beta-adrenoceptors.

Acetyl-CoA carboxylase has been purified from lactating rat mammary gland using a combination of ammonium sulphate and poly(ethyleneglycol) precipitations. The enzyme was purified from 35--70-fold with a yield of over 50%, the exact figures being difficult to estimate because of activation of the enzyme that occurs during the preparation. The preparation was homogeneous by the criterion of polyacrylamide gel electrophoresis in sodium dodecyl sulphate and had a single subunit of molecular weight 240,000, containing 1.02 +/- 0.04 molecules of biotin and 3.1 +/- 1.7 molecules of alkali-labile phosphate per subunit. The purified enzyme was phosphorylated and inactivated rapidly when incubated in the presence of [gamma 32P]ATP and magnesium ions with the purified catalytic subunit of cyclic-AMP-dependent protein kinase from rabbit skeletal muscle. Both phosphorylation and inactivation are blocked by the heat-stable protein inhibitor of cyclic-AMP-dependent protein kinase, and can be reversed by incubation with purified protein phosphatase-1 from rabbit skeletal muscle. The inactivation by the protein kinase and reactivation by the protein phosphatase correlate with the near-stoichiometric phosphorylation and dephosphorylation of site(s) located in a single tryptic peptide. Phosphorylation does not affect the Km for substrates, but brings about a twofold decrease in V and a twofold increase in the apparent dissociation constant for the allosteric activator, citrate. We also present evidence that the activation of rabbit mammary acetyl-CoA carboxylase by protein phosphatase-1 described previously [Hardie and Cohen (1979) FEBS Lett. 103, 333-338] is due to dephosphorylation at site(s) which are not phosphorylated by either cyclic-AMP-dependent protein kinase or acetyl-CoA carboxylase kinase-2. These results suggest that the rapid inactivation of acetyl-CoA carboxylase, and hence fatty acid synthesis, by adrenaline in adipose tissue, or glucagon in the liver, is due to phosphorylation of the enzyme by cyclic-AMP-dependent protein kinase.

The effect of cytosolic free Mg2+ concentration on the regulation of myocardial function was studied by dialyzing isolated guinea pig ventricular myocytes with different internal Mg2+ concentrations [( Mg2+]i). We found that elevation of [Mg2+]i shortened the action potential and suppressed the Ca2+ current. Mean values recorded for action potential duration in cells dialyzed with solutions containing 0, 1.3, and 9.4 mM Mg2+ were 620 +/- 40, 400 +/- 25, and 60 +/- 10, respectively. The suppressive effect of [Mg2+]i on the action potential duration correlated significantly with the suppressive effects of [Mg2+]i on the Ca2+ current. In cells dialyzed with nominally zero Mg2+, calcium current was prominent (3.5 +/- 0.58 nA). At [Mg2+]i of 1.4 mM, calcium current was significantly smaller than in zero [Mg2+]i and was almost completely inhibited by dialysis of the cell with 9.4 mM Mg2+. The Mg2+-induced block of the Ca2+ current was due to steady-state inactivation of the high threshold calcium channel. The block was observed in the presence or absence of adenosine 3',5'-cylic monophosphate and was not reversed by elevation of external Ca2+ concentration, addition of adrenaline, or large negative potentials. These data suggest that cytosolic Mg2+ regulates Ca2+ channel activity by a novel mechanism, unrelated to its effect as a blocking particle of the open channel.

A study was carried out to determine the time course and degree of postoperative insulin resistance in patients undergoing elective abdominal surgery. Mean(s.e.m.) insulin sensitivity was determined before and on the first (n = 10), fifth, ninth and 20th (n = 5) days after elective open cholecystectomy using the normoglycaemic (4.7(0.1) mmol/l), hyperinsulinaemic (402(12)pmol/l) glucose clamp technique. Preoperative insulin sensitivity expressed as the M value varied from 2.3 to 8.2 mg per kg per min. The relative reduction in insulin sensitivity was most pronounced on the first day after surgery, at a mean(s.e.m.) of 54(2) per cent. Thereafter, a large variation between individuals was found during the course of recovery, and insulin sensitivity returned to normal 20 days after operation. On the first day after surgery, plasma concentrations of glucose, C peptide, noradrenaline and glucagon were slightly but significantly higher than before operation (P < 0.05), whereas insulin, growth hormone, cortisol and adrenaline levels were unaltered. Marked insulin resistance thus develops after elective upper abdominal surgery and persists for at least 5 days after operation. Factors other than simultaneous changes in levels of the hormones studied seem to regulate the maintenance of postoperative insulin resistance.

BACKGROUND

Allergic reactions to food are well recognized in both children and adults, but because of their relative infrequency their typical features may not be readily recognized by patients and their medical care givers who are not allergists.

OBJECTIVE

We sought to investigate the circumstances and clinical characteristics of food allergies in adults and children in the community.

METHODS

Self-completed questionnaire responses over a 6-month period from 109 members of the Anaphylaxis Campaign, the major British patient resource group for people who have suffered severe allergic reactions.

RESULTS

One hundred and nine respondents reported 126 reactions during the study period. Seventy-five were children (under 16 years, median age 6 years at the time of reaction). Predictably more boys than girls were reported to have had reactions but more women reported reactions than men (P<0.05). Although the groups were equally aware of their food allergies the children had undergone diagnostic tests more often (P<0.001). Foods were implicated in 112 (89%) of reports. Restaurants were implicated less often (14%) than in other series, probably reflecting British eating habits. Children with asthma reported more severe reactions than those without asthma (P=0.008), although frequency or severity of recent asthma symptoms was not associated with severity of allergic reaction reported. When available, self-injectable adrenaline was used in 35% of severe reactions and 13% of non-severe reactions (P=0.01). A quarter of adults who received one dose of adrenaline also received a second dose.

CONCLUSIONS

The allergens implicated in this report reflect previous data from similar patient groups in North America. Asthmatic children suffer more severe reactions than non-asthmatic children. It appears that British adults need better access to expert care of their allergies. Even when it is prescribed and available self-injectable adrenaline appears under-used in severe reactions. The incidence of severe but non-fatal allergic reactions in the UK may have been underestimated in the past.

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting women of reproductive age; it is associated with hyperandrogenism, hyperinsulinemia, and dyslipidemia. This study was designed to assess the long term effects of a pure androgen receptor blocker, flutamide, on the lipid profile in women with PCOS and to examine the possible mechanisms by which androgens may exert their influence. Seventeen women with PCOS (10 obese and 7 lean) were studied. All subjects received a 12-week course of oral flutamide (500 mg/day). The baseline and posttreatment evaluations included lipid profile, androgen levels, insulin sensitivity, and serum catecholamine determinations. The primary outcome was the change in the ratio of low density lipoproteins (LDL) to high density lipoproteins (HDL). Treatment with flutamide was associated with a significant decrease in the LDL/HDL ratio by 23% (P = 0.005), in total cholesterol by 18% (P < 0.0001), in LDL by 13% (P = 0.002), and in triglycerides by 23% (P = 0.002). Flutamide treatment was also associated with a trend toward an increase in HDL (by 14%; P = 0.14). The effects on lipid profile were found regardless of obesity and were not associated with a change in weight. Furthermore, actions of flutamide on lipid metabolism were not associated with significant changes in circulating adrenaline or noradrenaline, glucose metabolism, or insulin sensitivity. This report has demonstrated for the first time that treatment with the pure antiandrogen, flutamide, may improve the lipid profile and that this effect may be due to direct inhibition of androgenic actions.

1. The effect of stimulation or inhibition of active Na-K transport on [(3)H]ouabain binding has been investigated in isolated soleus muscles and adipocytes.2. In rat soleus muscle, the ouabain-sensitive component of (42)K influx was stimulated by insulin (100 m-u/ml.), adrenaline (6 x 10(-6)M), and by pre-incubation with veratrine (10(-5)M) or in a K-free buffer. In all of these instances, the rate of ouabain binding was increased by 41-113%. Conversely, pre-treatment with tetracaine (0.2 mM) decreased the (42)K-influx and diminished the rate of [(3)H]ouabain binding by 36%.3. Neither insulin, adrenaline or tetracaine produced any detectable change in the total number of ouabain-binding sites (as measured under equilibrium conditions) in rat soleus muscle.4. In mouse and guinea-pig soleus muscle and in fat cells isolated from rats, insulin also increased the rate of [(3)H]ouabain binding without producing any significant change in the total number of ouabain-binding sites.5. Both in soleus muscle and the epididymal fat pad of the rat, there was a linear correlation between (42)K influx and the initial rate of [(3)H]ouabain binding.6. It is concluded that the rate of ouabain binding is determined significantly by the rate of active Na-K transport, but within the time intervals studied (4-6 hr) stimulation or inhibition of the Na pump does not lead to any appreciable change in the total number of Na pumps. It seems unlikely that the stimulation of active Na-K transport by insulin or adrenaline is due to unmasking or de novo synthesis of Na pumps.

The complications of failure, neural injury and local anaesthetic toxicity are common to all regional anaesthesia techniques, and individual techniques are associated with specific complications. All potential candidates for regional anaesthesia should be thoroughly evaluated and informed of potential complications. If there is significant risk of injury, then these techniques should be avoided. Central neural blockade (CNB) still accounts for more than 70% of regional anaesthesia procedures. Permanent neurological injury is rare (0.02 to 0.07%); however, transient injuries do occur and are more common (0.01 to 0.8%). Pain on injection and paraesthesiae while performing regional anaesthesia are danger signals of potential injury and must not be ignored. The incidence of systemic toxicity to local anaesthetics has significantly reduced in the past 30 years, from 0.2 to 0.01%. Peripheral nerve blocks are associated with the highest incidence of systemic toxicity (7.5 per 10000) and the lowest incidence of serious neural injury (1.9 per 10000). Intravenous regional anaesthesia is one of the safest and most reliable forms of regional anaesthesia for short procedures on the upper extremity. Brachial plexus anaesthesia is one of the most challenging procedures. Axillary blocks are performed most frequently and are safer than supraclavicular approaches. Ophthalmic surgery is particularly suited to regional anaesthesia. Serious risks include retrobulbar haemorrhage, brain stem anaesthesia and globe perforation, but are uncommon with skilled practitioners. Postdural puncture headache remains a common complication of epidural and spinal anaesthesia; however, the incidence has decreased significantly in the past 2 to 3 decades from 37 to approximately 1%, largely because of advances in needle design. Backache is frequently linked with CNB; however, other causes should also be considered. Duration of surgery, irrespective of the anaesthetic technique, seems to be the most important factor. The syndrome of transient neurological symptoms is a form of backache that is associated with patient position and use of lidocaine (lignocaine). Disturbances of micturition are a common accompaniment of CNB, especially in elderly males. Hypotension is the most common cardiovascular disturbance associated with CNB. Severe bradycardia and even cardiac arrest have been reported in healthy patients following neuraxial anaesthesia, with a reported incidence of cardiac arrest of 6.4 per 10 000 associated with spinal anaesthesia. Prompt diagnosis, immediate cardiopulmonary resuscitation and aggressive vasopressor therapy with epinephrine (adrenaline) are required. New complications of regional anaesthesia emerge occasionally, e.g. cauda equina syndrome with chloroprocaine, microspinal catheters and 5% hyperbaric lidocaine, and epidural haematoma formation in association with low molecular weight heparin. Even so, after 100 years of experience, most discerning physicians appreciate the benefits of regional anaesthesia.

beta-adrenergic receptors (beta-ARs) were identified in CG-5 breast cancer cells using a radiometric assay. The total beta-AR concentration was measured using the highly potent beta-adrenergic antagonist (-)[3H]CGP 12177, and the densities of beta-AR subtypes were discriminated in the presence of highly selective unlabelled ligands (CGP 20712A and ICI 118551). Scatchard analysis revealed good linearity (r>> 0.95) and Kd values (0.05-1 nM) indicated the presence of high affinity binding sites in CG-5 cell membranes. beta 2-AR concentrations (74%) were significantly (P < 0.05) higher than beta 1-AR concentrations (36%). Displacement studies indicated that tested adrenergic agonists displaced (-) [3H]CGP 12177 from its specific binding sites in the order of potency (-)isoproterenol>> (+/-)clenbuterol>> (-)adrenaline>> (+/-)dobutamine>>>> (-)noradrenaline, whereas beta-adrenergic antagonists inhibited the binding in the following order of potency: (-)propranolol>>>> ICI 118 551>>>> CGP 20712A. The functionality of beta-ARs identified in CG-5 cell membranes was demonstrated by the significant increase in cAMP production induced by different concentrations of isoproterenol vs unstimulated cells (control). The pathophysiological role of beta-ARs in breast cancer cells is still undefined, but their presence suggests the possible adrenergic regulation of some cellular activities such as proliferation and/or differentiation.

To compare the analgesic efficacy of local aesthetic with and without dexamethasone in supraclavicular brachial plexus block.

METHODS

Forty patients undergoing arm, forearm and hand surgeries were randomly selected. The forty patients were divided in two groups of 20 each. In-group one, a brachial plexus block was done with 40-50 ml of local anaesthetic with 1:200,000 adrenaline and in the other group the block was performed with the same amount of local anaesthetics with dexamethasone. The onset of action and duration of analgesia in the two groups were compared and any complications of the procedure were noted. Statistical analysis was done using the independent sample t-test.

RESULTS

The two groups were comparable in respect to age, sex, and weight. There was significant faster onset of action and prolonged duration of analgesia in the dexamethasone group than in the other group. There were no complications.

CONCLUSIONS

Addition of dexamethasone for brachial plexus block significantly prolongs the duration of analgesia without any unwanted effects.