Chemical composition and antimicrobial activity of the leaf essential oil of Skimmia laureola growing wild in Jammu and Kashmir, India.

The analysis of Skimmia laureola hydrodistillate by gas chromatography coupled with mass spectrometry revealed the presence of 20 constituents, representing 94.6% of the total oil. The major constituents of oil were linalyl acetate (33.0%), linalool (25.0%), limonene (8.1%), α-terpineol (5.9%) and geranyl acetate (5.9%). The monoterpene (93.4%) rich essential oil was evaluated for its antibacterial and antifungal activities against seven microorganisms by agar diffusion and microdilution methods. The oil showed appreciable antimicrobial effects against all Gram-positive bacteria tested, including methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis with MIC values 32 and 64 µg mL(-1), respectively. The oil also exhibited strong fungicidal activity against Aspergillus niger and Penicillium chrysogenum with MIC value in the range 32-16 µg mL(-1). The oil could be used in the formulation of antimicrobial agents.

Comparison of the growth hormone, IGF-1 and insulin in cerebrospinal fluid and serum between patients with motor neuron disease and healthy controls.

Neurotrophic effects of the growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin on the central nervous system have become more apparent in the past decade. In this study, we measured serum and cerebrospinal fluid (CSF) concentrations of GH, IGF-1 and insulin in 35 patients with motor neuron disease (MND) [24 patients with definite amyotrophic lateral sclerosis (ALS) and 11 patients with progressive bulbar palsy] and in 40 healthy controls. Levels of serum concentrations of GH and IGF-1 did not significantly differ between the MND patient group and the healthy controls, while the level of insulin was significantly decreased (P = 0.0033) in the MND patient group. However, levels of all three examined parameters in CSF were significantly lower in the MND group than in the healthy controls with the statistical significance for IGF-1 and insulin of P < 0.001. This finding has not been reported previously, and further investigations into its association with ALS should establish whether it can be used as an early marker of the disease, or whether it merely represents a consequence of ALS development.

MEAD: an interdisciplinary study of the marine effects of atmospheric deposition in the Kattegat.

This paper summarises the results of the EU funded MEAD project, an interdisciplinary study of the effects of atmospheric nitrogen deposition on the Kattegat Sea between Denmark and Sweden. The study considers emissions of reactive nitrogen gases, their transport, transformations, deposition and effects on algal growth together with management options to reduce these effects. We conclude that atmospheric deposition is an important source of fixed nitrogen to the region particularly in summer, when nitrogen is the limiting nutrient for phytoplankton growth, and contributes to the overall eutrophication pressures in this region. However, we also conclude that it is unlikely that atmospheric deposition can, on its own, induce algal blooms in this region. A reduction of atmospheric nitrogen loads to this region will require strategies to reduce emissions of ammonia from local agriculture and Europe wide reductions in nitrous oxide emissions.

Assessment of war and accidental nerve injuries in children.

Eleven children with war-related peripheral nerve injury and 16 children with accident-related nerve injury between the ages of 3 and 15 years were assessed clinically and electromyoneurographically for 1-15 months. Lesions of 32 peripheral nerves were registered in children with war injuries. Children with accidentally acquired injuries had lesions of 27 peripheral nerves. A complete loss of voluntary motor unit potentials and signs of total axonal damage were recorded in the upper arms of seven of 11 children with war injuries and in five of 16 children with accidental injuries. There was a diminished number of motor unit potentials and a reduction in compound muscle action potential amplitudes, indicating partial nerve lesions, in 11 of 16 children with accidental injuries (mostly after humeral fracture) and in three of 11 children with brachial plexus war injuries. Reinnervation signs first occurred after 5-9 months (mean = 6.2 months) in war-injured children receiving conservative treatment and after 2-7 months (mean = 3.4 months) in children with accidentally acquired injuries. War-related peripheral nerve injuries in children are more frequently associated with complete denervation followed by slower or delayed nerve regeneration. In children with accidentally acquired nerve injuries the course is significantly better.

[Treatment of Guillain-Barré syndrome]. / Lijecenje Guillain-Barréova sindroma.

The purpose of this article is to review the most up-to-date information on the treatment of Guillain-Barré syndrome-acute polyradiculoneuritis. Several different treatments for GBS are currently under investigation-plasmapheresis (plasma exchange), high-dosed intravenous gammaglobulin and intravenous corticosteroids. Controlled trials have shown that treatment with plasmapheresis reduced the time spent on a ventilator, in the intensive care unit, and the time needed to regain independent walking. It is generally accepted that plasmapheresis is indicated in severe GBS and for patients who are still in the first two weeks of the disease. High-dosed intravenous immunoglobulins showed their efficacy, at a dosage of 0.4 g/kg/daily for five days. The treatment is easier and morbidity is lower, but both therapies are very expensive. Corticosteroids cannot be considered useful therapy for GBS after two randomized controlled trials, one using conventional doses and the other high doses--500 mg methylprednisolone daily for five days. One pilot study on 25 patients has shown that combined treatment with high dose methylprednisolone and immunoglobulins was more effective than immunoglobulins alone. In the treatment of chronic polyradiculoneuritis corticosteroids do have a place. General medical care and supportive therapy in the intensive care unit are of the greatest importance.

Insurmountable beta receptor blockade by ICI 147,798 in rabbits.

In rabbits, the characteristics of cardiac beta-1 receptor blockade produced by ICI 147,798, a novel beta receptor blocking agent with diuretic properties, were evaluated and compared with those of propranolol. In conscious rabbits, i.v. injections of 0.31, 1.0 and 3.1 mg/kg of ICI 147,798 and 1.0 mg/kg of propranolol caused significant bradycardia. ICI 147,798 produced a dose-dependent shift to the right of the dose-response (chronotropic) curve of isoproterenol with suppression of the maximal tachycardia, an effect characteristic of insurmountable beta receptor blockade. Propranolol also produced a shift to the right of the dose-response curve of isoproterenol without affecting the maximal tachycardia. ICI 147,798-induced antagonism was specific for beta adrenoceptors as it failed to modify the effects of acetylcholine, angiotensin II, phenylephrine, adenosine, histamine and prostaglandin E2 on mean arterial pressure and heart rate. In rabbits with prior autonomic blockade, ICI 147,798, like propranolol, failed to inhibit the positive chronotropic effects of theophylline which are mediated by postreceptor mechanisms. In reserpinized rabbits, ICI 147,798 was found to have no intrinsic sympathomimetic activity. Unlike the effects of propranolol, which were attenuated by first-pass through the hepatic vascular bed, the effects of ICI 147,798 were unaffected suggesting an absence of first-pass metabolism. The effects of propranolol (1.0 mg/kg i.v.) were not detectable at 24 hr after injection, whereas significant beta receptor blocking activity was still present at 24 hr after ICI 147,798 (1.0 mg/kg i.v.). The results suggest that ICI 147,798 is a specific, long-acting, insurmountable beta-1 receptor blocking agent without intrinsic sympathomimetic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular pharmacology of ASL-8052, an ultra-short acting beta blocker.

ASL-8052, a novel ultra-short acting beta receptor blocking agent, was infused i.v. and its cardiovascular effects were investigated in conscious, as well as anesthetized rabbits. On i.v. infusion, its effects reached a steady state within 6 min and on termination of infusion, complete recovery occurred within 20 min. In conscious rabbits it inhibited isoproterenol-induced tachycardia and hypotension. There was more pronounced inhibition of the cardioaccelerator effects of isoproterenol than its hypotensive effects. ASL-8052 produced dose dependent bradycardia in conscious rabbits which was more marked in rabbits pretreated with atropine methyl nitrate. When infused in larger doses, a significant decrease in mean arterial pressure was seen in conscious as well as anesthetized rabbits. This hypotensive effect was not blocked by prior beta receptor blockade with propranolol. ASL-8052-induced hypotension was found to be due to a significant decrease in total peripheral resistance. It also produced vasodilation in the mesenteric vascular bed. The role of the liver in the clearance of ASL-8052 was investigated. When infused into the portal vein, the response to ASL-8052 was markedly attenuated, while an equivalent dose infused into the femoral vein produced a significant level of beta receptor blockade. These results suggest that ASL-8052 is an ultra-short acting beta receptor blocking agent with vasodilator effects in rabbits. While the liver may play a significant role in the clearance of ASL-8052 from circulation, the role of extra-hepatic mechanisms in the rapid decay of its pharmacological effects remains to be investigated.

Pentobarbital-induced changes in vagal tone and reflex vagal activity in rabbits.

The effects of pentobarbital on heart rate, reflexly mediated vagal activity and the automaticity (intrinsic rate) of the sinoatrial (SA) node were investigated in rabbits. When administered in three cumulative doses (10 mg/kg i.v. each) at 15 min intervals, each dose produced transient hypotension which was not modified by prior muscarinic receptor blockade (MRB), beta-receptor blockade (BRB), or combined MRB and BRB. Subanesthetic doses (10 mg/kg) of pentobarbital produced tachycardia in normal rabbits, as well as in rabbits with prior BRB. After pentobarbital, MRB failed to increase the heart rate, indicating total loss of resting vagal tone. Failure to induce tachycardia in rabbits with prior MRB indicated the absence of sympathetic stimulation in pentobarbital-induced tachycardia. In rabbits with prior BRB, pentobarbital enhanced the hypotensive effects of acetylcholine and nitroglycerin and abolished nitroglycerin-induced tachycardia without significant effects on the magnitude of reflex bradycardia produced by norepinephrine. Pentobarbital had minimal, transient depressant effects on the intrinsic rate of the SA node. These results indicate that pentobarbital produces total loss of resting vagal tone without major impairment of reflex vagal activation.