Characterization of the antinociceptive and sedative effect of amitraz in horses

Amitraz, an acaricide used to control ectoparasites in animals has a complex pharmacological activity, including α2-adrenergic agonist action. The purpose of this research was to investigate the possible antinociceptive and/or sedative effect of amitraz in horses. The sedative effect of the intravenous (i.v.) injection of dimethylformamide (DMF, 5 mL, control) or amitraz (0.05, 0.10, 0.15 mg/kg), was investigated on the head ptosis test. The participation of α2-adrenergic receptors in the sedative effect provoked by amitraz was studied by dosing yohimbine (0.12 mg/kg, i.v.). To measure the antinociception, xylazine hydrochloride (1 mg/kg, i.v., positive control) and the same doses of amitraz and DMF were used. A focused radiant light/heat directed onto the fetlock and withers of a horse were used as a noxious stimulus to measure the hoof withdrawal reflex latency (HWRL) and the skin twitch reflex latency (STRL). The three doses of amitraz used (0.05, 0.10 and 0.15 mg/kg) provoked a dose-dependent relaxation of the cervical muscles. The experiments with amitraz and xylazine on the HWRL showed that after i.v. administration of all doses of amitraz there was a significant increase of HWRL up to 150 min after the injections. Additionally, there was a significant difference between control (DMF) and positive control (xylazine) values up to 30 min after drug injection. On the other hand, the experiments on the STRL show that after administration of amitraz at the dose of 0.15 mg/kg, a significant increase in STRL was observed when compared with the control group. This effect lasted up to 120 min after injection. However, no significant antinociceptive effect was observed with the 0.05 and 0.10 mg/kg doses of amitraz or at the 1.0 mg/kg dose of xylazine.

The effect of non-antihypertensive doses of angiotensin converting enzyme inhibitor on myocardial necrosis and hypertrophy in young rats with renovascular hypertension

In renovascular hypertensive rats, low doses of angiotensin converting enzyme (ACE) inhibitors have been found to prevent myocardial hypertrophy independent of blood pressure level. This finding would suggest humoral rather than mechanical control of myocyte growth. The aim of this study was to examine the effect of nonantihypertensive doses of ACE inhibitor on myocardial hypertrophy and necrosis in hypertensive rats. Renovascular hypertension (RHT) was induced in four-week-old Wistar rats. Twenty-eight animals were treated for four weeks with three doses of ramipril (0.01, 0.1 or 1.0 mg/kg/day, which are unable to lower blood pressure. Fourteen animals were not treated (RHT group). A sham operated, age/sex-matched group was used as control (n=10). Myocardial histology was analysed in 3 μm thick sections of the ventricle stained with either haematoxylin-eosin, reticulin silver stain or Masson's trichrome. There was a significant correlation between systolic blood pressure and left ventricular to body weight ratio in both sets of animals: untreated plus controls and ramipril-treated rats. ACE inhibition prevented myocyte and perivascular necrosis and fibrosis in a dose-dependent manner. We conclude that myocardial hypertrophy in rats with renovascular hypertension is directly related to arterial pressure, and that this relationship is not affected by nonantihypertensive doses of ACE inhibitor. Myocardial necrosis/fibrosis and coronary artery damage induced by angiotensin II are prevented by ACE inhibitor in a dose-dependent manner, despite the presence of arterial hypertension.

The effects of Chlorella vulgaris in the protection of mice infected with Listeria monocytogenes. Role of natural killer cells

In this work we have demonstrated the effects of oral administration of Chlorella vulgaris (CV) on Natural Killer cells (NK) activity of mice infected with a sublethal dose of viable Listeria monocytogenes. The treatment with C. vulgaris produced a significant increase on NK cells activity in normal (non-infected) animals compared to the animals that received only vehicle (water) (p < 0.0001). Similarly, the infection alone produced a significant increase on NK cells activity, which was observed at 48 and 72 hours after the inoculation of L. monocytogenes. Moreover, when CV was administered in infected animals, there was an additional increase in NK cells activity which was significantly higher than that found in the infected groups (p < 0.0001) CV treatment (50 and 500mg/Kg) of mice infected with a dose of 3x105 bacteria/animal, which was lethal for all the non- treated controls, produced a dose-response protection which led to a 20% and 55% survival, respectively (p < 0.0001).

Pharmacological evidence for β2-adrenoceptor in right atria from stressed female rats

The purpose of the present study was to demonstrate a physiological response to TA2005, a potent β2-adrenoceptor (β2-AR) selective agonist, in right atria isolated from stressed female rats under the influence of the estrous cycle. We obtained concentration-response curves to the agonist in the presence and in the absence of selective antagonists in right atria isolated from female rats submitted to three daily foot-shock sessions (30 min duration, 120 pulses of 1.0 mA, 1.0 s, applied at random intervals of 5- 25 s) and sacrificed at estrus or diestrus. Our results showed that the pD2 values of TA2005 were not influenced by estrous cycle phase or foot-shock stress. However, in right atria from stressed rats sacrificed during diestins, the concentration-response curve to TA2005 was biphasic, with a response being obtained at concentrations of 0.1 nM, whereas during estrus no response was observed at doses lower than 3 nM. ICI118,551, a β2-AR antagonist, abolished the response to nanomolar concentrations of TA2005 in right atria from stressed rats at diestrus, with no changes in agonist pD2 values in right atria from control rats (7.47 ± 0.09, p > 0.05) but a 3-fold decrease in pD2 values of TA2005 in right atria from foot shock stressed rats (7.90 ± 0.07, p ≤ 0.05). Concentration-response curves to TA2005 in the presence of ICI118,551 were best fitted by a one-site model equation. The β1-AR antagonist, CGP20712A, shifted to the right only the second part of the concentration-response curves to the agonist, unmasking the putative β2-AR-mediated response to the agonist in tissues isolated from stressed rats at diestrus. Under this condition, concentration-response curves to the agonist were best fitted by a two-site model equation, pD2 and maximum response of TA2005 interaction with β1- and putative β2-adrenoceptor components were calculated. Schild analyses gave a pK(B) value for CGP20712A that was typical for the interaction with β1-AR in each experimental group, pK(B) values for ICI118,551 could not be obtained in stressed rats sacrificed at diestins since Schild plot slopes were lower than 1.0. In right atria from control rats, ICI118,551 pK(B) values were similar to reported values for the interaction of the antagonist with β1-AR. These results confirm that a heterogenous β1-AR population mediating the chronotropic response to catecholamines can be demonstrated in right atria from foot shock stressed female rats sacrificed at diestins. The stress-induced response seems to be mediated by the β2-AR subtype. Right atria from rats sacrificed during estrus are protected against stress-induced alterations on the homogeneity of β-AR population.

Titulacao do sevoflurano utilizando o indice bispectral em anestesia pediatrica. Influencia da medicacao pre-anestesica no tempo de despertar e no consumo de anestesico inalatorio

Background and Objectives - Sevoflurane is an inhalational anesthetic drug with low blood/gas solubility providing fast anesthesia induction and emergence. Its ability to maintain cardiovascular stability makes it ideal for pediatric anesthesia. The aim of this study was to evaluate hemodynamic stability, consumption of inhalational anesthetics and emergence time in children with and without premedication (midazolam or clonidine) anesthetized with sevoflurane titrated according to BIS monitoring. Methods - Participated in this study 30 patients aged 2 to 12 years, physical status ASA I, undergoing elective surgeries who were divided into 3 groups: G1 - without premedication, G2 - 0.5 mg.kg-1 oral midazolam, G3 - 4 μg.kg-1 oral clonidine 60 minutes before surgery. All patients received 30 μg.kg-1 alfentanil, 3 mg.kg-1 propofol, 0.5 mg.kg-1 atracurium, sevoflurane in different concentrations monitored by BIS (values close to 60) and N2O in a non rebreathing system. Systolic and diastolic blood pressure, heart rate, expired sevoflurane concentration (EC), sevoflurane consumption (ml.min-1) and emergence time were evaluated. Emergence time was defined as time elapsed between the end of anesthesia and patients' spontaneous movements trying to extubate themselves, crying and opening eyes and mouth. Results - There were no differences among groups as to systolic and diastolic blood pressure, EC, sevoflurane consumption and emergence time. Heart rate was lower in G3 group. Conclusions - Sevoflurane has provided hemodynamic stability. Premedication with clonidine and midazolam did not influence emergence time, inhaled anesthetic consumption or maintenance of anesthesia with sevoflurane. Anesthesia duration has also not influenced emergence time. Hypnosis monitoring was important for balancing anesthetic levels and this might have been responsible for the similarity of emergence times for all studied groups.

Tempo de latencia e duracao do efeito do brometo de rocuronio no paciente submetido ao transplante renal

Background and Objectives - Successful cadaver kidney transplantation relies on a fast procedure. Patients with chronic renal failure may present with a delayed gastric emptying making it critical a fast tracheal intubation and airway maintenance. Rocuronium a recently introduced nondepolarizing neuromuscular blocker with a fast onset. The aim of this study was to evaluate onset time and duration of rocuronium effects in patients undergoing renal transplantation. Methods - Sixty patients were allocated into two groups of 30: Group R (GR) = patients undergoing renal transplantation and Group N (GN) = patients with normal renal function. All patients were premedicated with oral midazolam (15 mg) and anesthesia was induced with 30 μg.kg-1 alfentanil, 0.3 mg.kg-1 etomidate and 0.6 mg.kg-1 rocuronium injected through a central venous catheter. neuromuscular block was monitored by acceleromyography in the ulnar nerve pathway. The following parameters were evaluated: time between administration of rocuronium and first twitch reduction to 5% after supra-maximal stimulation (T1) (onset time = OT); time for first twitch to return to 25% (clinical duration = R25); time elapsed between 25% and 75% recovery of first twitch (relaxation recovery time = R25-75). Heart rate (HR) and mean blood pressure (MBP) were recorded in 6 moments. Results - Median OT was 31 sec. in GR and 47 sec. in GN. Median R25 was 51.5 min in GR and 33.5 min in GN. Median R25-75 was 28 min in GR and 20 min in GN. MBP and HR were higher in GR. Tracheal intubation conditions were excellent for most patients in both groups. Conclusions - These results open the possibility of 0.6 mg.kg-1 rocuronium being injected through a central venous catheter when a faster onset is needed. Due to wide differences in individual responses, monitoring of neuromuscular block is recommended.

Influence of antimicrobial subinhibitory concentrations on hemolytic activity and bacteriocin-like substances in oral: Fusobacterium nucleatum

Fusobacterium nucleatum is considered for its role in colonization of initial and late microorganisms in dental plaque and for its coaggregation with other bacterial species. It is known that action of different antimicrobial substances may interfere with either virulence factors or with host-bacteria interaction. The goal of this study was to examine the influence of subinhibitory concentrations of chlorhexidine, triclosan , penicillin G and metronidazole on hemolytic activity and bacteriocin-like substance production of oral F. nucleatum. A high resistance to penicillin G was observed and 63% of the isolates were β-lactamase positive. All the tested isolates were susceptible to metronidazole. F. nucleatum isolates grown with or without antimicrobials were alpha-hemolytics. Bacteriocin-like substance production was increased in isolates grown with penicillin G. Impaired production of hemolytic or antagonic substances can suggest a role in the regulation of oral microbiota.

Effects of ethanol on human visual evoked potentials

Studies of the effect of ethanol on human visual evoked potentials are rare and usually involve chronic alcoholic patients. The effect of acute ethanol ingestion has seldom been investigated. We have studied the effect of acute alcoholic poisoning on pattern-reversal visual evoked potentials (PR-VEP) and flash light visual evoked potentials (F-VEP) in 20 normal volunteers. We observed different effects with ethanol: statistically significant prolonged latencies of F-VEP after ingestion, and no significant differences in the latencies of the PR-VEP components. We hypothesize a selective ethanol effect on the afferent transmission of rods, mainly dependent on GABA and glutamatergic neurotransmission, influencing F-VEP latencies, and no effect on cone afferent transmission, as alcohol doesn't influence PR-VEP latencies.

Efeito do extrato aquoso de sete-sangrias [Cuphea mesostemon (Koehne) Lourt] sobre o fluxo de água, medido em bexiga urinária de sapo in vitro

The Cuphea mesostemon specie, known as sete-sangrias, is widely used as a diuretic substance in popular medicine. As the toad urinary bladder is an epithelium analogous to the distal nephron of mammals, it is used in order to study the transport water and electrolytes in many laboratories. This preparation permits excellent observation in water flow, from the urinary bladder lumen to the external side or the serosal one (water re-absorption), by means of gravimetrical measures. In the present work the hydrosmotic effect of aqueous extract (AE) of sete-sangrias leaf was studied. A 20% solution was added to the serosal side (S) of the bladder preparation, and the water flow was measured every 15 minutes after that. The results showed that 4mL of AE in the S side, increased the JH20 in a significant manner (p<0,05). This effect had a dose - response shape, with the volumes of 0,2mL, 0,4mL and 0,8mL of AE in the S bath. The hydro-osmotic effect of the anti-diuretic hormone (ADH) was studied as well and a significant stimulation (p<0,05) in the JH2O was observed with the magnitude of 150%. The AE effect was similar to the ADH one, and was not antagonized by this hormone. We concluded that Cuphea possesses an anti-diuretic activity similar to that presented by ADH, in toad urinary bladder, in vitro.

Organophosphate induced delayed neuropathy in genetically dissimilar chickens: Studies with tri-ortho-cresyl phosphate (TOCP) and trichlorfon

Measurements of plasma cholinesterase (pl.ChE), brain cholinesterase (Br.ChE) and brain Neuropathy Target Esterase (Br.NTE) were made in three different lineages of chickens. All birds received toxicants through gavage in a single oral dose between 08:00 and 09:00 h, after overnight fast. Babcock chickens were treated with 800 mg/kg tri-ortho-cresyl phosphate (TOCP) or 80 mg/kg trichlorfon. The TOCP group had 82% Br.NTE inhibition, when compared to the control group, and no birds displayed symptoms of clinical organophosphate-induced delayed neuropathy (OPIDN). Hy-line w36 lineage chickens were given 1600 mg/kg TOCP and despite this higher dose, Br.NTE inhibition was similar that presented by Babcock chickens. Isabrown chickens were given 1600 mg/kg TOCP or 80 mg/kg trichlorfon. At 36 h all trichlorfon treated birds had from 80 to 90% inhibition of Pl.ChE and Br.ChE, when compared to controls. However, Br.NTE was inhibited less than 20%, and there were no clinical signs of OPIDN. All TOCP treated isabrown chickens had more than 80% Br.NTE inhibition while one of them exhibited just light signs of OPIDN, two chickens became totally paralyzed. This finding suggested that chicken strain was important in the appearance of OPIDN. In addition, 70-80% of NTE inhibition was necessary but was not sufficient to produce OPIDN in chickens, since babcock and hy-line w36 chickens exhibited NTE inhibition in the range of 70-80% without clinical signs of OPIDN. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

Study on the mutagenicity and antimutagenicity of a natural food colour (annatto) in mouse bone marrow cells

Most manufactured foods contain chemicals added as a deliberate part of the manufacturing process. The aims of the present study were to evaluate the mutagenicity and antimutagenicity of annatto, a natural pigment extracted from the Bixa orellana L. and widely used as a colorant in foods. The micronucleus test was performed in bone marrow cells from Swiss male mice treated with one of the three concentrations of annatto (1330, 5330 and 10,670 ppm), incorporated into the diet. The animals were fed with the diets for 7 days and sacrificed 24 h after the last treatment. For the evaluation of the antimutagenic potential of annatto, at day 7, the animals received an intraperitoneal injection of cyclophosphamide (50 mg/kg body weight). Under the concentrations tested annatto did not present mutagenic or antimutagenic activities on the mice bone marrow cells. However, an increased frequency of micronucleated cells was observed when the highest concentration (10,670 ppm) was administered simultaneously with cyclophosphamide. In conclusion, the data indicate that annatto colour, for the conditions used, is neither mutagenic nor an inhibitor of induced mutations, although it should be used carefully since high doses may increase the effect of a mutagen. © 2003 Elsevier Science Ltd. All rights reserved.

Effects of contrast material on computed tomographic measurements of lung volumes in patients with acute lung injury

Background. Intravenous injection of contrast material is routinely performed in order to differentiate nonaerated lung parenchyma from pleural effusion in critically ill patients undergoing thoracic computed tomography (CT). The aim of the present study was to evaluate the effects of contrast material on CT measurement of lung volumes in 14 patients with acute lung injury. Method. A spiral thoracic CT scan, consisting of contiguous axial sections of 10 mm thickness, was performed from the apex to the diaphragm at end-expiration both before and 30 s (group 1; n=7) or 15 min (group 2; n=7) after injection of 80 ml contrast material. Volumes of gas and tissue, and volumic distribution of CT attenuations were measured before and after injection using specially designed software (Lungview®; Institut National des Télécommunications, Evry, France). The maximal artifactual increase in lung tissue resulting from a hypothetical leakage within the lung of the 80 ml contrast material was calculated. Results. Injection of contrast material significantly increased the apparent volume of lung tissue by 83 ± 57 ml in group 1 and 102 ± 80 ml in group 2, whereas the corresponding maximal artifactual increases in lung tissue were 42 ± 52 ml and 31 ± 18 ml. Conclusion. Because systematic injection of contrast material increases the amount of extravascular lung water in patients with acute lung injury, it seems prudent to avoid this procedure in critically ill patients undergoing a thoracic CT scan and to reserve its use for specific indications.

Poisoning of mice by Baccharis coridifolia: An experimental model

The poisonous plant Baccharis coridifotia causes necrosis in lymphoid tissues and the gastrointestinal tract of cattle, horses, sheep and rabbits. An experimental poisoning of mice was undertaken to establish an experimental model in a laboratory animal specie. A single 5 to 8-g/kg dose of a suspension of the plant was administered by gavage to II mice. To 3 other control mice, the same volume of water was administered. Plant-dosed mice manifested clinical effects after 12 h: tachipnea, trembles, dehydration and prostration. Most of the dosed mice died 14 to 33 h after plant administration-3 survived for 12 d. Six mice had remarkable necrosis of the germinative center of secondary follicles in lymph nodes and spleen; 3 mice had necrosis of lymphoid tissues in intestine and thymus. Mice reproduce most of the lesions observed in naturally poisoned cattle and the use of this specie as an experimental model is valid.

A novel biological activity for galectin-1: Inhibition of leukocyte-endothelial cell interactions in experimental inflammation

Galectin-1 (Gal-1), the prototype of a family of β -galactoside-binding proteins, has been shown to attenuate experimental acute and chronic inflammation. In view of the fact that endothelial cells (ECs), but not human polymorphonuclear leukocytes (PMNs), expressed Gal-1 we tested here the hypothesis that the protein could modulate leukocyte-EC interaction in inflammatory settings. In vitro, human recombinant (hr) Gal-1 inhibited PMN chemotaxis and trans-endothelial migration. These actions were specific as they were absent if Gal-1 was boiled or blocked by neutralizing antiserum. In vivo, hrGal-1 (optimum effect at 0.3 μg equivalent to 20 pmol) inhibited interleukin-1β-induced PMN recruitment into the mouse peritoneal cavity. Intravital microscopy analysis showed that leukocyte flux, but not their rolling velocity, was decreased by an anti-inflammatory dose of hrGal-1. Binding of biotinylated Gal-1 to resting and post-adherent human PMNs occurred at concentrations inhibitory in the chemotaxis and transmigration assays. In addition, the pattern of Gal-1 binding was differentially modulated by PMN or EC activation. In conclusion, these data suggest the existence of a previously unrecognized function of Gal-1, that is inhibition of leukocyte rolling and extravasation in experimental inflammation. It is possible that endogenous Gal-1 may be part of a novel anti-inflammatory loop in which the endothelium is the source of the protein and the migrating PMNs the target for its anti-inflammatory action.

Effect of the Clinical Application of the GaA1As Laser in the Treatment of Dentine Hypersensitivity

Objective: The aim of this study was to evaluate the effectiveness of the clinical use of the gallium-aluminum-arsenium (GaAlAs) laser at the maximum and minimum energies recommended by the manufacturer for the treatment of dentine hypersensitivity. Background Data: Dentine hypersensitivity (DH) is a response to a stimulus that would not usually cause pain in a healthy tooth. It is characterized by sharp pain of short duration from the denuded dentin. Its etiology is unknown. The dentin only begins to show sensitivity when exposed to the buccal environment. This exposure can result after removal of the enamel and/or dental cement, or after root denudation. Different treatments are proposed for this disorder. Materials and Methods: In this study, 25 patients, with a total number of 106 cases of DH, were treated with GaAlAs low-level laser therapy (LLLT). 65% of the teeth were premolars; 14% were incisors and molars; 6.6% were canines. The teeth were irradiated with 3 and 5 J/cm 2 for up to six sessions, with an interval of 72 h between each application, and they were evaluated initially, after each application, and at 15 and 60 days follow-up post-treatment. Results: The treatment was effective in 86.53% and 88.88% of the irradiated teeth, respectively, with the minimum and maximum energy recommended by the manufacturer. There was a statistically significant difference between DH and after a follow-up of 60 days for both groups. The difference among the energy maximum and minimum was not significant. Conclusion: The GaAlAs low-level laser was effective in reducing initial DH. A significant difference was found between initial values of hypersensitivity and after 60 days follow-up post-treatment. No significant difference was found between minimum (3 J/cm 2) and maximum (5 J/cm 2) applied energy.