Homing behaviour by destructive crown-of-thorns starfish is triggered by local availability of coral prey.

Corallivorous crown-of-thorns starfishes (Acanthaster spp.) can decimate coral assemblages on Indo-Pacific coral reefs during population outbreaks. While initial drivers of population irruptions leading to outbreaks remain largely unknown, subsequent dispersal of outbreaks appears coincident with depletion of coral prey. Here, we used in situ time-lapse photography to characterize movement of the Pacific crown-of-thorns starfish (Acanthaster cf. solaris) in the northern and southern Great Barrier Reef in 2015, during the fourth recorded population outbreak of the starfish, but prior to widespread coral bleaching. Daily tracking of 58 individuals over a total of 1117 h revealed all starfish to move a minimum of 0.52 m, with around half of all tracked starfish showing negligible daily displacement (less than 1 m day-1), ranging up to a maximum of 19 m day-1. Movement was primarily nocturnal and daily displacement varied spatially with variation in local availability of Acropora spp., which is the preferred coral prey. Two distinct behavioural modes emerged: (i) homing movement, whereby tracked paths (as tested against a random-walk-model) involved short displacement distances following distinct 'outward' movement to Acropora prey (typically displaying 'feeding scars') and 'homebound' movement to nearby shelter; versus (ii) roaming movement, whereby individuals showed directional movement beyond initial tracking positions without return. Logistic modelling revealed more than half of all tracked starfish demonstrated homing when local abundance (percentage cover) of preferred Acropora coral prey was greater than 33%. Our results reveal facultative homing by Acanthaster with the prey-dependent behavioural switch to roaming forays providing a mechanism explaining localized aggregations and diffusion of these population irruptions as prey is locally depleted.

Impaired mitochondrial oxidative phosphorylation in the peroxisomal disease X-linked adrenoleukodystrophy.

X-linked adrenoleukodystrophy (X-ALD) is an inherited metabolic disorder of the nervous system characterized by axonopathy in spinal cords and/or cerebral demyelination, adrenal insufficiency and accumulation of very long-chain fatty acids (VLCFAs) in plasma and tissues. The disease is caused by malfunction of the ABCD1 gene, which encodes a peroxisomal transporter of VLCFAs or VLCFA-CoA. In the mouse, Abcd1 loss causes late onset axonal degeneration in the spinal cord, associated with locomotor disability resembling the most common phenotype in patients, adrenomyeloneuropathy. We have formerly shown that an excess of the VLCFA C26:0 induces oxidative damage, which underlies the axonal degeneration exhibited by the Abcd1(-) mice. In the present study, we sought to investigate the noxious effects of C26:0 on mitochondria function. Our data indicate that in X-ALD patients' fibroblasts, excess of C26:0 generates mtDNA oxidation and specifically impairs oxidative phosphorylation (OXPHOS) triggering mitochondrial ROS production from electron transport chain complexes. This correlates with impaired complex V phosphorylative activity, as visualized by high-resolution respirometry on spinal cord slices of Abcd1(-) mice. Further, we identified a marked oxidation of key OXPHOS system subunits in Abcd1(-) mouse spinal cords at presymptomatic stages. Altogether, our results illustrate some of the mechanistic intricacies by which the excess of a fatty acid targeted to peroxisomes activates a deleterious process of oxidative damage to mitochondria, leading to a multifaceted dysfunction of this organelle. These findings may be of relevance for patient management while unveiling novel therapeutic targets for X-ALD.

The decrease of NAD(P)H has a prominent role in dopamine toxicity.

We characterized dopamine toxicity in human neuroblastoma SH-SY5Y cells as a direct effect of dopamine on cell reductive power, measured as NADH and NADPH cell content. In cell incubations with 100 or 500 microM dopamine, the accumulation of dopamine inside the cell reached a maximum after 6 h. The decrease in cell viability was 40% and 75%, respectively, after 24 h, and was not altered by MAO inhibition with tranylcypromine. Dopamine was metabolized to DOPAC by mitochondrial MAO and, at 500 microM concentration, significantly reduced mitochondrial potential and oxygen consumption. This DA concentration caused only a slight increase in cell peroxidation in the absence of Fe(III), but a dramatic decrease in NADH and NADPH cell content and a concomitant decrease in total cell NAD(P)H/NAD(P)+ and GSH/GSSG and in mitochondrial NADH/NAD+ ratios. Dopaminechrome, a product of dopamine oxidation, was found to be a MAO-A inhibitor and a strong oxidizer of NADH and NADPH in a cell-free system. We conclude that dopamine may affect NADH and NADPH oxidation directly. When the intracellular concentrations of NAD(P)H and oxidized dopamine are similar, NAD(P)H triggers a redox cycle with dopamine that leads to its own consumption. The time-course of NADH and NADPH oxidation by dopamine was assessed in cell-free assays: NAD(P)H concentration decreased at the same time as dopamine oxidation advanced. The break in cell redox equilibrium, not excluding the involvement of free oxygen radicals, could be sufficient to explain the toxicity of dopamine in dopaminergic neurons.

Clindamycin vs penicillin for anaerobic lung infections. High rate of penicillin failures associated with penicillin-resistant Bacteroides melaninogenicus.

Thirty-seven adult patients with anaerobic lung infections (27 lung abscesses and 10 necrotizing pneumonias) were submitted to transthoracic needle-aspiration and/or bronchoscopic specimen brush cultures before therapy and thereafter in all cases considered to be failures. Patients were randomly assigned to receive either clindamycin, 600 mg intravenously every 6 hours, or penicillin G, 2 million U every 4 hours for no less than 8 days, until clinical and radiological improvement became apparent. Treatment was continued orally with clindamycin, 300 mg every 6 hours, or penicillin V, 750 mg every 6 hours, until completing a minimum of 4 weeks. Ten of the 47 anaerobes initially isolated from the lung (nine Bacteroides melaninogenicus and one Bacteroides capillosus) were resistant to penicillin, but none were resistant to clindamycin. Five of the nine patients harboring these penicillin-resistant Bacteroides received penicillin, and all failed to respond to therapy. Overall, eight of the 18 patients in the penicillin group and one of 19 in the clindamycin group failed to respond to therapy. These drugs were equally well tolerated in both groups. The presence of penicillin-resistant Bacteroides is a frequent cause of penicillin failure in patients with anaerobic lung infections. In this setting, clindamycin appears to be the current therapy of choice for initial treatment.

Activation of sirtuin 1 as therapy for the peroxisomal disease adrenoleukodystrophy.

Oxidative stress and mitochondrial failure are prominent factors in the axonal degeneration process. In this study, we demonstrate that sirtuin 1 (SIRT1), a key regulator of the mitochondrial function, is impaired in the axonopathy and peroxisomal disease X-linked adrenoleukodystrophy (X-ALD). We have restored SIRT1 activity using a dual strategy of resveratrol treatment or by the moderate transgenic overexpression of SIRT1 in a X-ALD mouse model. Both strategies normalized redox homeostasis, mitochondrial respiration, bioenergetic failure, axonal degeneration and associated locomotor disabilities in the X-ALD mice. These results indicate that the reactivation of SIRT1 may be a valuable strategy to treat X-ALD and other axonopathies in which the control of redox and energetic homeostasis is impaired.

Cells overexpressing fructose-2,6-bisphosphatase showed enhanced pentose phosphate pathway flux and resistance to oxidative stress.

Changes in the content of fructose-2,6-bisphosphate, a modulator of glycolytic flux, also affect other metabolic fluxes such as the non-oxidative pentose phosphate pathway. Since this is the main source of precursors for biosynthesis in proliferating cells, PFK-2/FBPase-2 has been proposed as a potential target for neoplastic treatments. Here we provide evidence that cells with a low content of fructose-2,6-bisphosphate have a lower energy status than controls, but they are also less sensitive to oxidative stress. This feature is related to the activation of the oxidative branch of the pentose phosphate pathway and the increased production of NADPH.

Antagonism of the stimulant and depressant effects of ethanol in rats by naloxone.

The action of naloxone (0.5 and 2 mg/kg IP) on the behavioural effects of a low (2 g/kg PO) and a high dose (4 g/kg PO) of ethanol was studied in rats. Ethanol at the low dose increased spontaneous motility, enhancing open-field external ambulations and reducing shuttle-box latency. All these effects were antagonized by naloxone. Ethanol at the high dose produced by hypomotility, decreasing open-field external ambulations and impairing shuttle-box performance. In this case, naloxone also reduced the ethanol effect, but its action was less consistent. Therefore, although mechanisms other than a specific opioid receptor blockade by naloxone must be considered, an involvement of opioid peptides in the effects of ethanol cannot be discounted.

Inhibitory and contractile effects of okadaic acid on rat uterine muscle.

The effects of okadaic acid and its interactions with various agents known to increase, by different mechanisms, the intracellular levels of cyclic AMP and/or cyclic GMP were investigated in isolated strips of rat myometrium. Okadaic acid showed inhibitory effects at concentrations between 10(-7) M and 3 x 10(-6) M. At higher concentrations, a biphasic, contractile and then relaxant response was observed. The results obtained suggest that, in rat uterine smooth muscle, the inhibitory effects of okadaic acid are not entirely mediated by the activation of cyclic AMP- and/or cyclic GMP-dependent pathways. The data also point to the existence of a clear interaction between okadaic acid and methylxanthines, although further studies are needed to clarify the mechanisms involved in this interaction.

Chronic amitriptyline decreases autotomy following dorsal rhizotomy in rats.

In the rat, unilateral dorsal cervicothoracic rhizotomy (C5-T1), a proposed model of chronic pain, resulted in autotomy of the ipsilateral limb. The self-mutilation lesions were evaluated daily by means of an autotomy score from the 1st to the 80th postoperatory day. The onset of lesions was variable and attained the maximum degree 8-9 weeks after the dorsal roots section. Chronic administration of amitriptyline (5 and 10 mg/kg/day, i.p., over 30 days), started on the 10th day after rhizotomy, decreased autotomy behavior, an effect which persisted 20 days after treatment withdrawal, and lengthened almost two-fold the lag time between rhizotomy and appearance of lesions. A more pronounced effect was observed with the lowest dose of amitriptyline suggesting the existence of a therapeutic window. Possible mechanisms for the antinociceptive effect of amitriptyline in this model are discussed.

Therapeutic effects of hidrosmin on chronic venous insufficiency of the lower limbs.

A double-blind, placebo-controlled trial was carried out to assess the effectiveness of a new synthetic bioflavonoid, hidrosmin, in patients with chronic venous insufficiency of the lower limbs. Fifty-seven patients, showing varicose veins and ankle swelling and suffering from local pain and heaviness of the legs, were allocated at random to receive treatment for 45 days with 1 capsule 3-times daily of either 200 mg hidrosmin (30 patients) or placebo (27 patients). Pain and heavy legs were assessed using rating scales; swelling was assessed by a photographic method. The results showed that hidrosmin produced a significant clinical improvement in all of the parameters evaluated; compared with placebo, there was a marked reduction in the main subjective symptoms accompanied by a 10% reduction in swelling. Apart from 1 patient who complained of epigastric pain, there were no reports of adverse events during the study period.

Pharmacological study of the muscle paralyzing activity of the juice of the banana trunk.

Extracts of the juice of the banana trunk were assayed in the isolated phrenic nerve-diaphragm muscle preparation of the rat. The chemical composition of those producing muscular paralysis was then studied. As active extracts mainly consisted of monopotassium oxalate, the effect of this compound on the muscle preparation was investigated and compared with that of the active extracts. The pattern of muscular paralysis induced by monopotassium oxalate was the same as that seen with the juice extracts. Likewise inhibition of contractions of the tibialis muscle was observed in vivo after intra-arterial administration of both the crude concentration of the juice and monopotassium oxalate. These findings suggest that monopotassium oxalate could be responsible for the muscular paralysis caused by the juice of banana trunk.

Effect of naloxone on behavioral changes induced by subchronic administration of ethanol in rats.

Endogenous opioid peptides appear to be involved in acute behavioral effects induced by single doses of ethanol. However, its role in repeated ethanol exposure has not been studied. In the present study ethanol was given to rats at the doses of 2 and 4 g/kg by a stomach gauge for 15 days, and its effects on spontaneous motility, open-field activity, and active avoidance behavior recorded on the 3rd, the 6th and the 15th days. Then the effect of naloxone (0.5 and 2 mg/kg by intraperitoneal route) was tested against a challenge ethanol dose, administrated by oral route, on the 16th day. Control animals received tap water and saline instead of ethanol or naloxone, respectively. Both doses of ethanol induced a decrease in spontaneous motility that was antagonized by naloxone. Open-field ambulations were increased by the high dose of ethanol, low-dose lacking effect; naloxone did not modify these ethanol effects. The low dose of ethanol shortened latency time in shuttlebox, the high dose causing escape and freezing responses; none of these effects were modified by naloxone. Therefore, endogenous opioid peptides appear to play a limited role in the chronic effects of ethanol in rats; particularly its effects in tests inducing an increase in the level of anxiety were resistant to naloxone.

Effect of ethanol on insulin-stimulated glucose uptake in the isolated rat diaphragm.

Insulin-stimulated (0.16 and 2.56 nM) glucose uptake (GU) was studied in isolated rat diaphragms in the presence of ethanol (EtOH) 21, 42 and 84 mM as well as in diaphragms removed from rats orally treated with the drug (1.5 or 4.5 g/kg/day) for 10 or 30 days. In spite of inhibiting the base-line GU, the addition of EtOH to the incubation medium gave rise to a potentiation of the insulin effect. In the orally intoxicated series, the low-dose EtOH increased the response to 0.16 nM insulin after 10 or 30 days, no changes being observed in that induced by 2.56 nM insulin. On the other hand, the high-dose EtOH caused an increase of the base-line GU which remained practically unmodified in the presence of insulin. The precise molecular basis for these phenomena is unknown.

Diuretic action of an aqueous extract of Lepidium latifolium L.

An aqueous extract of Lepidium latifolium L. given orally and intraperitoneally considerably enhanced urinary excretion (UV) in rats with respect to control groups. A slight increase in ion excretion was also observed. Other parameters such as specific gravity, nitrite, pH, glucose, ketone bodies, urobilinogen, and blood were also studied. A good correlation for the dosage rat/man for the aqueous extract was achieved.

Adverse drug reactions in paediatric outpatients.

In accordance with guidelines for a multicentre trial, the incidence and features of adverse drug reactions in a sample of 1327 children attending outpatient consultations have been determined. The incidence was of 0.75% (0.34% - 1.58% with p less than 0.05). The reactions were slight in character and predominantly affected very young female patients. Antibiotics were involved in almost a half of cases, and polypharmacy was used in all of them.

[Conservative treatment of 2 tracheal lesions secondary to anesthetic intubation]. / Tratamiento conservador en dos lesiones traqueales secundarias a intubación anestésica.

This case report describes two patients admitted to our hospital for elective surgery, one for biliary disease and the other for vascular disease. Shortly after surgery each presented a clinical picture attributable to membranous tracheal pars rupture caused by anesthetic intubation. Airway lesions were diagnosed and, after patient status was evaluated, conservative medical treatment was prescribed in both cases. Outcome was excellent, with no complications, within a few days. These cases demonstrate the efficacy of this way of managing this potentially serious complication.

[Continuous epidural perfusion with meperidine on demand for the treatment of postoperative pain]. / Perfusión continua más demanda de meperidina por vía peridural en el tratamiento del dolor postoperatorio.

OBJECTIVE: To determine whether epidural administration of meperidine through a system affording patient-controlled analgesia (PCA) is appropriate for postoperative pain. PATIENTS AND METHODS: A prospective double-blind study of 30 patients undergoing high abdominal surgery randomly into two groups. After surgery with the same type of general anesthesia for both groups, group A received epidural meperidine through a PCA pump (initial boluses of 50 mg + infusion of 10 mg/h with additional doses of 25 mg upon patient demand and closure time of 90 min). Control group B received 0.9% saline serum through an epidural PCA system with identical perfusion characteristics. All patients had access to additional analgesia with subcutaneous meperidine (1 mg/kg weight). RESULTS: There was a wide interindividual variation in meperidine consumption in group A, with a mean total dose of 301.4 +/- 73 mg in 24 hours and no patient requiring additional subcutaneous meperidine. Subcutaneous meperidine required in group B reached 273 +/- 65.8 mg in 24 hours, with no significant differences between groups A and B for total dose given. No side effects inherent to the technique were found. Sufficient control of pain was achieved for all patients receiving epidural meperidine. CONCLUSIONS: Epidurally administered PCA with meperidine affords better pain relief with greater patient satisfaction than the same amount of drug given subcutaneously in successive doses upon patient request.