The intracellular signaling pathway of octopamine upregulating immune resistance functions in Penaeus monodon.

Octopamine (OA), a biogenic monoamine, is known to mediate several immune responses. This study analyzed the effects of OA on immunological regulation in the tiger shrimp Penaeus monodon. The immune parameters including total haemocyte count, differential haemocyte count, phenoloxidase activity, respiratory bursts, superoxide dismutase activity, and phagocytic activity and clearance efficiency in response to the pathogen, Photobacterium damselae, were determined when shrimp were individually injected with saline or OA at 100 or 1000 pmol shrimp-1. In addition, the intracellular second messengers in haemocyte such as Ca2+ and adenosine 3',5'-cyclic monophosphate (cAMP) were examined in shrimp receiving saline or OA at 1 or 10 nmol shrimp-1. Results showed that all of the immune parameters significantly increased at 2-4 h in OA-injected shrimp except hyaline cells in 100 pmol shrimp-1-injected shrimp at 4 h, but phenoloxidase activity per granulocyte significantly decreased at 2-4 h. However, these had returned to saline control levels after receiving OA for 8 h except differential haemocyte count and phenoloxidase activity per granulocyte for 16 h. An injection of OA also significantly increased the survival rate of shrimp challenged with Pho. damselae. Shrimp receiving OA at 1 and 10 nmol shrimp-1 significantly increased the intracellular Ca2+ concentration ([Ca2+]i) at 30-60 min and 30 min, and cAMP concentration [cAMP]i) at 5-15 min and 15 min, respectively. However, [Ca2+]i at 50-60 min, and [cAMP]i at 30-60 min returned to saline control when the shrimp received OA at 10 nmol shrimp-1, and at 1 and 10 nmol shrimp-1, respectively. These results suggest that OA administration by injection at ≤1000 pmol shrimp-1 mediates transient upregulation of immunity together with the increased resistance of P. monodon to Pho. damselae, which are modulated through intracellular Ca2+ and cAMP second messenger pathways.

Dexmedetomidine as an Additive to Local Anesthesia: A Step to Development in Dentistry.

PURPOSE: The study aimed to compare the effect of dexmedetomidine added to lidocaine against epinephrine added to lidocaine on local anesthetic potency and to look for future prospects of dexmedetomidine as an additive to local anesthesia in dentistry. MATERIALS AND METHODS: The study included 25 healthy volunteers in whom extraction of all first premolars was scheduled as part of their orthodontic treatment plan. In this split-mouth, double-blind, crossover, randomized controlled trial, patients were randomized into 2 groups: Group 1 received injection lidocaine plus dexmedetomidine, and group 2 was administered lidocaine plus epinephrine. Patients were assessed for the onset of action of anesthesia, duration of analgesia, pain perception, and vital signs. RESULTS: The mean values (±standard deviations) for the onset of anesthetic action in groups 1 and 2 were 113 ± 24.9 and 141 ± 34.8 seconds, respectively, for the mandible. For the maxilla, the mean values were 113 ± 24.9 seconds for group 1 and 165 ± 43.8 seconds for group 2. The duration of anesthesia was longer in group 1 (lidocaine plus dexmedetomidine), in which the requirement for the first analgesic on request was seen after a longer time interval, when compared with group 2 (lidocaine plus epinephrine). Pain perception elicited statistically significant results with less perception of pain in group 1 (lidocaine plus dexmedetomidine). The vital parameters remained stable, and the results were not statistically significant. CONCLUSIONS: In this study, we observed that the addition of dexmedetomidine to lidocaine for maxillary and mandibular nerve blocks significantly prolonged the block duration and shortened the onset of action, as well as improved postoperative analgesia in terms of the need for fewer analgesics in the postoperative period. Furthermore, the vital parameters remained stable and no complications were encountered. The findings were supportive of the use of dexmedetomidine as an adjunct to local anesthetics in dental procedures.

[Classification of local anesthesia methods]. / Klassifikatsiya sposobov mestnoi anestezii.

The traditional classification methods of dental local anesthesia must be modified. In this paper we proved that the vascular mechanism is leading component of spongy injection. It is necessary to take into account the high effectiveness and relative safety of spongy anesthesia, as well as versatility, ease of implementation and the growing prevalence in the world. The essence of the proposed modification is to distinguish the methods in diffusive (including surface anesthesia, infiltration and conductive anesthesia) and vascular-diffusive (including intraosseous, intraligamentary, intraseptal and intrapulpal anesthesia). For the last four methods the common term «spongy (intraosseous) anesthesia¼ may be used.

Devices and topical agents for rosacea management.

Rosacea is a chronic inflammatory disease that predominantly affects facial skin in light-skinned individuals and can be divided into 4 subtypes. Patients can display signs of more than 1 subtype. Diffuse facial erythema is a common finding in rosacea patients and can lead to persistent erythema. Although there is no cure for rosacea, reduction of signs and symptoms can be achieved via various treatment modalities. This article reviews devices and topical agents currently available for the management of rosacea.

Intrathecal clonidine and baclofen enhance the pain-relieving effect of spinal cord stimulation: a comparative placebo-controlled, randomized trial.

OBJECTIVE: Spinal cord stimulation (SCS) is a well-established treatment for neuropathic pain; nevertheless, 40% of patients fail to obtain satisfactory pain relief and in many patients, the effect tends to diminish with time. Based on animal experiments, intrathecal baclofen was previously introduced clinically to enhance suboptimal SCS effects. Later animal experiments demonstrated similar data for clonidine. The aim of this study was to elucidate whether intrathecal clonidine or baclofen enhances the effect of SCS in neuropathic pain patients in whom the pain relieving-effect of SCS is inadequate. METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted with 10 patients experiencing neuropathic pain with insufficient pain relief with SCS alone. Clonidine, baclofen, and saline (control) were intrathecally administered by bolus injections in combination with SCS. RESULTS: Seven of 10 patients reported significant pain reduction when SCS was combined with active drugs. The mean visual analog scale ratings were reduced by more than 50% with either drug combined with SCS. Four patients previously treated with SCS alone later underwent implantation of a pump for long-term administration of clonidine or baclofen. In the 2 patients with clonidine pumps with a mean follow-up of 15 months, the combined therapy produced pain reduction of 55% and 45%, respectively. The corresponding effect with baclofen was 32% and 82%, respectively, at 7 months follow-up. CONCLUSION: A trial with clonidine and baclofen combined with SCS may be warranted in patients who do not obtain satisfactory pain relief with SCS alone or experienced a decreasing therapeutic effect.

Dexmedetomidine blocks thermal hyperalgesia and spinal glial activation in rat model of monoarthritis.

AIM: To investigate the effect of systemic administration dexmedetomidine, a selective alpha 2 adrenergic receptor (alpha(2)AR) agonist, on thermal hyperalgesia and spinal glial activation evoked by monoarthritis (MA). METHODS: MA was induced by an intra-articular injection of complete Freund's adjuvant (CFA). Thermal hyperalgesia was measured by Hargreaves' test. The spinal glial activation status was analyzed by GFAP (an astrocytic marker) and Iba-1 (a microglial marker) immunohistochemistry or immunoblotting. RESULTS: Unilateral intra-articular injection of CFA produced a robust glial activation of astrocytes and microglia in the spinal cord, which was associated with the development and maintenance of thermal hyperalgesia. Intraperitoneal (ip) injection of dexmedetomidine (2.5 and 10 microg/kg) was repeatedly given once daily for 5 days with the first injection 60 min before intra-articular CFA. At the dose of 10 microg/kg, dexmedetomidine significantly attenuated MA-induced ipsilateral hyperalgesia from day 2 to day 5. MA-induced up-regulation of GFAP expression on both sides of the spinal dorsal horn was significantly suppressed by day 5 post-MA following dexmedetomidine application, whereas MA-induced Iba-1 up-regulation was only partially suppressed. CONCLUSION: Systemic dexmedetomidine inhibits the activation of spinal glia, which is possibly associated with its antihyperalgesia in monoarthritic rats.

Physiologic effects of electroacupuncture combined with intramuscular administration of xylazine to provide analgesia in goats.

OBJECTIVE: To investigate physiologic effects of electroacupuncture (EA) combined with xylazine administration in goats. ANIMALS: 48 healthy crossbred goats. PROCEDURES: Goats were randomly allotted to 8 groups of 3 (nonpregnant and nonlactating) female goats and 3 male goats each. The 8 treatment groups were as follows: 1 EA group, 3 xylazine (0.1, 0.2, and 0.4 mg/kg, IM) groups, 3 EA plus xylazine (0.1, 0.2, and 0.4 mg/kg, IM) groups, and 1 control group. Electroacupuncture was performed for 90 minutes. Xylazine was administered 20 minutes after EA was performed. Pain threshold, heart rate, mean arterial pressure (MAP), respiration rate, and rectal temperature were observed at 0, 5, 25, 45, 65, and 85 minutes after xylazine administration. RESULTS: Xylazine administered at 0.4 mg/kg increased the pain threshold and reduced MAP. Xylazine administered at 0.1, 0.2, or 0.4 mg/kg reduced heart rate, respiration rate, and temperature. Electroacupuncture increased the pain threshold but had no effect on heart rate, MAP, respiratory rate, or rectal temperature. Pain threshold in goats that underwent EA plus xylazine administration was higher than in goats that received EA or xylazine alone. Electroacupuncture combined with xylazine at 0.1 mg/kg did not affect heart rate, MAP, respiratory rate, or rectal temperature. Pain threshold in goats that underwent EA plus xylazine administration at 0.1 mg/kg was higher than in goats given xylazine at 0.4 mg/kg alone. CONCLUSIONS AND CLINICAL RELEVANCE: Electroacupuncture combined with xylazine, even at 0.1 mg/kg, provided analgesia without significantly affecting cardiorespiratory parameters or rectal temperature in goats.

Clonidine as an adjunct therapy to opioids for neonatal abstinence syndrome: a randomized, controlled trial.

OBJECTIVE: To determine if oral clonidine would reduce the duration of opioid detoxification for neonatal abstinence syndrome. METHODS: Infants with intrauterine exposure to methadone or heroin and neonatal abstinence syndrome (2 consecutive modified Finnegan scores of > or =9) were enrolled at 2 hospitals during 2002-2005 and followed until final hospital discharge. All enrolled infants (80) received oral diluted tincture of opium according to a standardized algorithm and were randomly assigned to receive oral clonidine (1 microg/kg every 4 hours) (40 infants) or placebo (40 infants). Primary outcome was duration of opioid therapy. Secondary outcomes included the amount of opium required to control symptoms, number of treatment failures, and differences in blood pressure, heart rate, and oxygen saturation. RESULTS: The median length of therapy was 27% shorter in the clonidine group (11 [95% confidence interval: 8-15 days]) than in the placebo group (15 days [95% confidence interval: 12-17 days]). In the clonidine group, 7 infants required restarting opium after initial discontinuation versus none in the placebo group, with the total length of treatment/observation remaining significantly less in the clonidine group. Higher dosages of opium were required by 40% of the infants in the placebo group versus 20% in the clonidine group. Treatment failures occurred in 12.5% of the infants in the placebo group versus none in the clonidine group. Hypertension, hypotension, bradycardia, or desaturations did not occur in either group. Three infants in the clonidine group died as a result of myocarditis, sudden infant death syndrome, and homicide, all after hospital discharge and before 6 months of age. CONCLUSIONS: In this randomized, double-blind trial, adding clonidine to standard opioid therapy for detoxification from in utero exposure to methadone or heroin reduced the duration of pharmacotherapy for neonatal abstinence without causing short-term adverse cardiovascular outcomes. A larger trial is indicated to determine long-term safety.

Conscious sedation during ophthalmic surgery under local anesthesia.

Sedation during ophthalmic local anesthesia helps to ensure comfort and cooperation during eye surgery. Sedation requirements of ophthalmic patients have changed with the popularization of newer surgical and anesthetic techniques. Many sedative agents are available to anesthesiologists including benzodiazepines, intravenous anesthetic induction agents, narcotic analgesics and a-adrenoreceptor agonists. However, there is no single ideal sedative agent, regime or protocol that can completely cater to the wide spectrum of ophthalmic procedures performed in a heterogeneous patient population. Moreover, the clinical practice of sedation during ophthalmic surgery under local anesthesia is varied and not without risk of complications and adverse events. Hence, balanced sedative techniques should only be used after careful consideration of patient profile, the type of eye surgery, and patient and surgeon preferences. Good knowledge of the pharmacology of sedative agents is fundamental to their useful clinical application.

Noradrenergic control of arginine vasopressin release from the ewe hypothalamus in vitro: sensitivity to oestradiol.

The present study aims at ascertaining the influence of alpha(1)-adrenoreceptors on arginine vasopressin (AVP) release in vitro and determine whether E(2) modulates the alpha(1)-adrenoreceptor and AVP interaction. Ten minutes after ewe killing, sagittal midline hypothalamic slices (from the anterior preoptic area to the mediobasal hypothalamus with the median eminence, 2 mm thick, 2 per sheep) were dissected, placed in oxygenated minimum essential media-alpha (MEM-alpha) at 4 degrees C and within 2 h were singly perifused at 37 degrees C with oxygenated MEM-alpha (pH 7.4; flow rate 0.15 ml/min), either with or without E(2) (24 pg/ml). After 4 h equilibration, 10 min fractions were collected for 4 h interposed with 10 min exposure at 60 min to a specific alpha(1)-adrenoreceptor agonist or antagonist at various doses (0.1-10 mm). At the end of all perifusions, slices responded to KCl (100 mm) with AVP efflux (p < 0.05). Release of AVP was enhanced (p < 0.05) by the alpha(1)-adrenoreceptor agonist (methoxamine 10 mm; no E(2), n = 7 perifusion chambers: from 14.3 +/- 2.7 to 20.9 +/- 3.9, with E(2), n = 10: from 10.7 +/- 1.2 to 18.4 +/- 3.4 pg/ml) or the antagonist (thymoxamine 10 mm; no E(2), n = 5: from 9.5 +/- 3.1 to 30.4 +/- 6.0, with E(2), n = 10: from 10.8 +/- 0.9 to 39.1 +/- 6.3 pg/ml). With the agonist, the response occurred only at 80 min (p < 0.05) both in the presence and absence of E(2). Whereas, after the antagonist, values were higher (p < 0.05) throughout the post-treatment period (80-170 min) without E(2), but declined by 150 min in the presence of E(2). Furthermore, the response to the alpha(1)-adrenoreceptor antagonist was greater (p < 0.05; 90-140 min) than the agonist only in the presence of E(2). In conclusion, these results reveal direct alpha(1)-adrenoreceptor-mediated control of the hypothalamic AVP neuronal system which is modulated by E(2).

The effects of dexmedetomidine on cardiac electrophysiology in children.

BACKGROUND: Dexmedetomidine (DEX) is an alpha2-adrenergic agonist that is approved by the Food and Drug Administration for short-term (<24 h) sedation in adults. It is not approved for use in children. Nevertheless, the use of DEX for sedation and anesthesia in infants and children appears to be increasing. There are some concerns regarding the hemodynamic effects of the drug, including bradycardia, hypertension, and hypotension. No data regarding the effects of DEX on the cardiac conduction system are available. We therefore aimed to characterize the effects of DEX on cardiac conduction in pediatric patients. METHODS: Twelve children between the ages of 5 and 17 yr undergoing electrophysiology study and ablation of supraventricular accessory pathways had hemodynamic and cardiac electrophysiologic variables measured before and during administration of DEX (1 microg/kg IV over 10 min followed by a 10-min continuous infusion of 0.7 microg x kg(-1) x h(-1)). RESULTS: Heart rate decreased while arterial blood pressure increased significantly after DEX administration. Sinus node function was significantly affected, as evidenced by an increase in sinus cycle length and sinus node recovery time. Atrioventricular nodal function was also depressed, as evidenced by Wenckeback cycle length prolongation and prolongation of PR interval. CONCLUSION: DEX significantly depressed sinus and atrioventricular nodal function in pediatric patients. Heart rate decreased and arterial blood pressure increased during administration of DEX. The use of DEX may not be desirable during electrophysiology study and may be associated with adverse effects in patients at risk for bradycardia or atrioventricular nodal block.

Dragon's blood from Croton urucurana (Baill.) attenuates visceral nociception in mice.

Dragon's blood, the red sap from Croton urucurana Baill. (Euphorbiaceae) has a profound history of traditional use in conditions such as inflammation, diarrhoea and gastrointestinal distress. Previous studies established its anti-inflammatory, antidiarrhoeal and analgesic properties and in this study we verified its potential to suppress visceral pain, using capsaicin- and cyclophosphamide-induced models of visceral nociception. Mice that received intra-colonic capsaicin (0.3%, 50 microl/animal) or intraperitoneal injection of cyclophosphamide (400 mg/kg) manifested spontaneous nociceptive behaviors or crises, which were significantly suppressed in animal groups treated with red sap (200 and 400 mg/kg, p.o.) or that received N-acetylcysteine (750 mg/kg, i.p.) or morphine (7.5 mg/kg, s.c.), as positive controls. In capsaicin model, the antinociception produced by 200 mg/kg red sap was found to be naloxone-sensitive (2 mg/kg, i.p.), suggesting an opioid mechanism. In tests of open-field and pentobarbital-sleeping time, mice received 200mg/kg red sap showed no significant alterations in either locomotion frequency or on sleeping time, indicating that the observed antinociception is not a consequence of sedation or motor abnormality. These findings highlight the visceral antinociceptive property of Croton urucurana sap and further support its ethno-medical use to alleviate pain associated with gastrointestinal and other related disorders.

Continuous infusion in adult females dogs submitted to ovariohysterectomy with midazolam-xylazine and/or medetomidine pre-treated with methotrimeprazine and buprenorphine

PURPOSE: To compare, by continuous infusion of ketamine or medetomidine combined to methotrimeprazine and buprenorphine, ketamine and midazolam, the degree of hypnosis, myorelaxation, anesthetic quality and surgical feasibility through evaluation of possible parametric alterations and recovery quality. METHODS: 20 healthy adult females dogs, aged 3 to 5 years, body weight between 7 and 15 kg, were assigned randomly and homogenously to 2 groups of 10 animals each (n=10), group 1 (G1) and group 2 (G2), respectively. Animals of G1 were subjected to a pre-treatment with intravenous 1.0 mg/kg methotrimeprazine and or 3ì/kg. After 15 minutes, a 5.0 mg/kg ketamine and 0.2 mg/kg midazolam were intravenously injected. Immediately after induction, an anesthetic combination of 0.4 mg/kg/h midazolam, 20 mg/kg/h ketamine and 1.0 mg/kg/h xylazine, was continuously and intravenously administered for 30 minutes. The same techniques were used in G2 except for the substitution of xylazine for 30ìg/kg/h medetomidine. RESULTS: In G1 there was a 1st and 2nd degree atrioventricular heart block, a longer recovery period and lower quality. In G2 a 1st degree atrioventricular heart block occurred but isolated and ephemeral. CONCLUSIONS: The continuous infusion method, besides reducing drugs utilization, prevented collateral effects allowing a more tranquil recovery with no excitations, both protocols permitted the surgical procedure (ovary-hysterectomy) bringing about a reduction in hypnosis and an accentuated myorelaxation. Xylazine and medetomidine showed a similar pharmacodynamic behavior but with different clinical aspects. The electrocardiographic alterations observed in G2 and in a lower degree in G1 must be well studied. Describers: dogs, ketamine, methotrimeprazine, medetomidine, midazolam and xylazine.

OBJETIVO: Comparar através de infusão contínua de xilazina ou medetomidina associada à metotrimeprazina e buprenorfina, cetamina e midazolam, o grau de hipnose, miorrelaxamento e qualidade anestésica e a viabilidade cirúrgica, avaliando eventuais alterações paramétricas e qualidade de recuperação. MÉTODOS: Foram utilizados 20 cães fêmeas, adultas, hígidas (3 a 5 anos de idade) com peso corporal entre 7 e 15 quilos, escolhidas e distribuídas aleatoriamente de forma homogênea em 2 grupos de 10 animais cada, (n=10) sendo estes designados por Grupo 1 (G1), e Grupo 2 (G 2). Em G1, os animais foram submetidos a um pré-tratamento com metotrimeprazina na dose de 1,0 mg/kg e buprenorfina na dose de 0,003mg/kg ou 3 µg/kg intravenoso. Decorridos 15 minutos, administrou-se cetamina na dose de 5,0 mg/kg e midazolam na dose de 0,2 mg/kg intravenoso. Imediatamente após a indução iniciou-se administração contínua, por um período de 30 minutos, da associação anestésica de midazolam 0,4 mg/kg/h, cetamina 20mg/kg/h e xilazina 1,0 mg/kg/h IV. Em G 2 utilizou-se a mesma técnica empregada em G1 substituindo-se, a xilazina pela medetomidina na dose de 30µg/kg/h. RESULTADOS: Verificou-se em G1 bloqueio átrio-ventricular de primeiro e segundo grau, período de recuperação mais longo além de menor qualidade. Em G 2 observou-se bloqueio átrio-ventricular de primeiro grau isolado e de ação fugaz. CONCLUSÕES: Ao se aplicar o método de infusão contínua, além da redução dos fármacos aplicados, evitaram-se efeitos colaterais permitindo uma recuperação mais tranqüila e isenta de excitações, ambos os protocolos permitiram a realização do ato cirúrgico (ovário-salpingo-histerectomia), causando uma redução da hipnose e um miorrelaxamento acentuado. A xilazina e a medetomidina apresentam um comportamento farmacodinâmico semelhante, porém com aspectos clínicos diferentes, as alterações eletrocardiográficas observadas em G 2 e em menor grau em G1 devem ser melhor estudadas.

Continuous infusion in adult females dogs submitted to ovariohysterectomy with midazolam-xylazine and/or medetomidine pre-treated with methotrimeprazine and buprenorphine.

PURPOSE: To compare, by continuous infusion of ketamine or medetomidine combined to methotrimeprazine and buprenorphine, ketamine and midazolam, the degree of hypnosis, myorelaxation, anesthetic quality and surgical feasibility through evaluation of possible parametric alterations and recovery quality. METHODS: 20 healthy adult females dogs, aged 3 to 5 years, body weight between 7 and 15 kg, were assigned randomly and homogenously to 2 groups of 10 animals each (n=10), group 1 (G1) and group 2 (G2), respectively. Animals of G1 were subjected to a pre-treatment with intravenous 1.0 mg/kg methotrimeprazine and or 3ì/kg. After 15 minutes, a 5.0 mg/kg ketamine and 0.2 mg/kg midazolam were intravenously injected. Immediately after induction, an anesthetic combination of 0.4 mg/kg/h midazolam, 20 mg/kg/h ketamine and 1.0 mg/kg/h xylazine, was continuously and intravenously administered for 30 minutes. The same techniques were used in G2 except for the substitution of xylazine for 30ìg/kg/h medetomidine. RESULTS: In G1 there was a 1st and 2nd degree atrioventricular heart block, a longer recovery period and lower quality. In G2 a 1st degree atrioventricular heart block occurred but isolated and ephemeral. CONCLUSIONS: The continuous infusion method, besides reducing drugs utilization, prevented collateral effects allowing a more tranquil recovery with no excitations, both protocols permitted the surgical procedure (ovary-hysterectomy) bringing about a reduction in hypnosis and an accentuated myorelaxation. Xylazine and medetomidine showed a similar pharmacodynamic behavior but with different clinical aspects. The electrocardiographic alterations observed in G2 and in a lower degree in G1 must be well studied. Describers: dogs, ketamine, methotrimeprazine, medetomidine, midazolam and xylazine.

Anti-emetic effect of oculo-acupuncture on dogs with xylazine induced vomiting.

The present study was conducted in order to clarify the anti-emetic effect of oculo-acupuncture (OA) on dogs with xylazine-induced vomiting, and also to compare the anti-emetic effect of OA and body acupuncture (AP). Twelve dogs induced to vomit by xylazine were selected from total 29 mongrel dogs in preliminary experiment and were used as subjects in this study. This study was comprised of two experiments. In experiment 1, the anti-emetic effects of OA on dogs were examined in the stomach/spleen region (experimental group I), the zhongjiao region (experimental group II), and the stomach/spleen region plus the zhongjiao region (experimental group III) using 12 dogs induced to vomit for one week interval repeatedly. On the other hand, needle acupuncture (AP) (BL20 + BL21, experimental group A) and OA (stomach/spleen and zhong jiao regions) combined with needle AP (BL20 + BL21) (experimental group B) were examined using 6 vomiting dogs, for one week interval repeatedly in experiment 2. As a result, the vomiting rates of experimental group I (50%, p < 0.05), experimental group II (58.3%) and experimental group III (41.6%, p < 0.01) were lower than that of control (100%), respectively in experiment 1. The vomiting rates of both experimental group A (50%, p < 0.05) and experimental group B (50%, p < 0.05) were lower than that of control (100%) in experiment 2. The starting vomiting time in experimental groups was similar to that of the control groups in experiment 1 and 2. This study demonstrated that OA had anti-emetic effects on dogs with xylazine-induced vomiting and OA in the stomach/spleen region plus the zhongjiao region was the most effective in anti-emesis among the experimental groups. In addition, body AP and OA combined with body AP had a similar anti-emetic effect on dogs with xylazine-induced vomiting.

Characterization of spinal alpha-adrenergic modulation of nociceptive transmission and hyperalgesia throughout postnatal development in rats.

BACKGROUND AND PURPOSE: The selective alpha(2)-adrenergic agonist dexmedetomidine is used clinically for analgesia and sedation, but effects in early life are not well characterized. Investigation of age-related effects of dexmedetomidine is important for evaluating responses to exogenously administered analgesics and provides insight into postnatal function of noradrenergic pathways. EXPERIMENTAL APPROACH: We examined effects of epidural dexmedetomidine in anaesthetized rat pups (3, 10 and 21 postnatal days) using a quantitative model of nociception and C-fibre induced hyperalgesia. Electromyographic recordings of withdrawal responses to hindpaw mechanical stimuli measured effects of dexmedetomidine upon the baseline reflex and the response to mustard oil application on the hindpaw (primary hyperalgesia) or hindlimb (secondary hyperalgesia). In addition, we compared epidural with systemic administration, examined effects of spinal transection and evaluated heart rate changes following dexmedetomidine. KEY RESULTS: Epidural dexmedetomidine dose-dependently prevented mustard oil-induced hyperalgesia at all ages but dose requirements were lower in the youngest pups. Higher doses also suppressed the baseline nociceptive reflex when given epidurally, but had no effect when given systemically. Analgesic efficacy was the same for primary and secondary hyperalgesia, and was not diminished by spinal cord transection. CONCLUSIONS AND IMPLICATIONS: Our laboratory studies predict that spinally mediated alpha(2)-agonist analgesia would be effective throughout postnatal development, dose requirements would be lower in early life and selective anti-hyperalgesic effects could be achieved with epidural administration at doses lower than associated with antinociceptive or cardiovascular effects. Clinical trials of alpha(2) agonists in neonates and infants should consider developmentally regulated changes.

Neuroprotective effects of brimonidine treatment in a rodent model of ischemic optic neuropathy.

Ischemic optic neuropathy (ION) is a common disorder caused by disruption of the arterial blood supply to the optic nerve. It can result in significant loss of visual acuity and/or visual field. An ischemic optic nerve injury was produced in rats by intravenous injection of Rose Bengal dye followed by argon green laser application to the retinal arteries overlying the optic nerve, causing a coagulopathy within the blood vessels and disruption of optic nerve and retinal perfusion. The effect of brimonidine tartrate eye drops on survival of retinal ganglion cell axons in this experimental paradigm was studied. One eye was treated and the contralateral eye served as a control. Four groups of animals were used for this study. Group 1 received 7 days of treatment with 0.15% brimonidine tartrate eye drops twice a day prior to the ischemic injury. Group 2 animals received 0.15% brimonidine tartrate eye drops twice a day for 14 days after photocoagulation injury. Animal groups 3 and 4 received eye drops of 0.9% NaCl twice a day either daily for 7 days before injury or daily for 14 days, respectively. All rats were sacrificed 5 months after the injury to ascertain long-term optic axon survival. Coagulopathy-induced optic nerve ischemia resulted in a 71% loss of optic axons. Treatment with brimonidine daily for the 7 days prior to the injury resulted in a greater survival of optic axons, with only a 56.1% loss compared to control. Brimonidine treatment every day for 14 days after the ischemic injury did not result in a significant rescue of optic axons compared to injury alone. In summary, the application of brimonidine eye drops for one week prior to an ischemic injury resulted in a statistically significant increase in survival of optic axons within the injured optic nerves. Brimonidine treatment of the eye after the ischemic injury did not result in axon rescue, and axon loss was similar to the injured optic nerves treated with saline only. These results suggest that brimonidine may have potential use for prevention of ION in at-risk patients.

Disruption of prepulse inhibition after stimulation of central but not peripheral alpha-1 adrenergic receptors.

Prepulse inhibition (PPI) refers to the attenuation of startle when a weak prestimulus precedes the startling stimulus. PPI is deficient in several psychiatric illnesses involving poor sensorimotor gating. Previous studies indicate that alpha1 adrenergic receptors regulate PPI, yet the extent to which these effects are mediated by central vs peripheral receptors is unclear. The present studies compared the effects of intracerebroventricular (ICV) vs intraperitoneal (IP) delivery of several alpha1 receptor agonists on PPI. Male Sprague-Dawley rats received either cirazoline (0, 10, 25, 50 microg/5 microl), methoxamine (0, 30, 100 microg/5 microl), or phenylephrine (0, 3, 10, 30 microg/5 microl) ICV immediately before testing. Separate groups received either cirazoline (0, 0.25, 0.50, 0.75 mg/kg), methoxamine (0, 2, 5, 10 mg/kg), or phenylephrine (0, 0.1, 2.0 mg/kg) IP 5 min before testing. PPI, baseline startle responses, and piloerection, an index of autonomic arousal, were measured. Cirazoline disrupted PPI; effective ICV doses were approximately six times lower than effective IP doses. Methoxamine disrupted PPI after ICV infusion but failed to affect PPI with IP doses that were up to 30-fold higher than the effective ICV dose. Phenylephrine disrupted PPI with ICV administration, but did not alter PPI after IP injection of even a 20-fold higher dose. None of the ICV treatments altered baseline startle magnitude, but phenylephrine and methoxamine lowered startle after administration of high systemic doses. Piloerection was induced by cirazoline via either route of administration, and by IP methoxamine and phenylephrine, but not by ICV infusion of methoxamine or phenylephrine. These findings indicate that alpha1 receptor-mediated PPI disruption occurs exclusively through stimulation of central receptors and is dissociable from alterations in baseline startle or autonomic effects.

Participation of alpha2 receptors in the antinociceptive activity of quercetin.

The present work was planned to evaluate the antinociceptive activity of quercetin, its site of action, and the involvement of adrenergic receptors in mediating the antinociceptive activity in thermal and chemonociceptive assays. Eight groups were employed in this study: Groups I, II, and III received quercetin alone in different doses, group IV animals were administered clonidine, group V animals were co-administered quercetin and clonidine, group VI animals were administered yohimbine 30 minutes prior to administratin of quercetin, group VII animals were administered yohimbine 30 minutes prior to co-administration of quercetin and clonidine, and group VIII animals were administered 0.5% carboxymethylcellulose in saline (vehicle for quercetin). The thermal nociception was measured by tail flick and hot plate methods. Quercetin produced a significant analgesic effect in a dose-dependent manner. Co-administration of low doses of quercetin and clonidine produced a synergistic analgesic effect. Pretreatment with yohimbine significantly reversed quercetin-as well as clonidine/quercetin combination-induced effects. The results of this study reveal that quercetin induces an antinociceptive effect and that this effect involves primarily the modulation of adrenergic pathways.

Métodos para abandono do tabagismo e tratamento da dependência da nicotina / Methods for smoking cessation and treatment of nicotine dependence

O tabagismo está relacionado a 30% das mortes por câncer. É fator de risco para desenvolver carcinomas do aparelho respiratório, esôfago, estômago, pâncreas, cérvix uterina, rim e bexiga. A nicotina induz tolerância e dependência pela ação nas vias dopaminérgicas centrais, levando às sensações de prazer e recompensa mediadas pelo sistema límbico. É estimulante do sistema nervoso central (SNC), aumenta o estado de alerta e reduz o apetite. A diminuição de 50% no consumo da nicotina pode desencadear sintomas de abstinência nos indivíduos dependentes: ansiedade, irritabilidade, distúrbios do sono, aumento do apetite, alterações cognitivas e fissura pelo cigarro. O aconselhamento médico é fundamental para o sucesso no abandono do fumo. A farmacoterapia da dependência de nicotina divide-se em: primeira linha (bupropiona e terapia de reposição da nicotina), e segunda linha (clonidina e nortriptilina). A bupropiona é um antidepressivo não-tricíclico que age inibindo a recaptação de dopamina, cujas contra-indicações são: epilepsia, distúrbios alimentares, hipertensão arterial não-controlada, abstinência recente do álcool e uso de inibidores da monoaminoxidase (MAO). A terapia de reposição de nicotina pode ser feita com adesivos e gomas de mascar. Os efeitos da acupuntura no abandono do fumo ainda não estão completamente esclarecidos. As estratégias de interrupção abrupta ou redução gradual do fumo têm a mesma probabilidade de sucesso.

Smoking is related to 30 percent of cancer deaths. It is a risk factor for respiratory tract, esophagus, stomach, pancreas, uterine cervix, kidney and bladder carcinomas. Nicotine induces tolerance and addiction by acting on the central dopaminergic pathways, thus leading to pleasure and reward sensations within the limbic system. It stimulates the central nervous system (CNS), enhances alertness and reduces the appetite. A 50 percent reduction of nicotine consumption may trigger withdrawal symptoms in addicted individuals: anxiety, anger, sleep disorders, hunger, cognitive dysfunction and cigarette craving. Medical advice is the cornerstone of smoking cessation. Pharmacotherapy of nicotine addiction comprises first-line (bupropion and nicotine replacement therapy) and second-line (clonidine and nortriptyline) drugs. Bupropion is a non-tricyclic antidepressant that inhibits dopamine uptake, whose contraindications are: epilepsy, eating disorders, uncontrolled hypertension, recent alcohol abstinence and current therapy with MAO inhibitors. Nicotine replacement therapy can be done with patches or gums. Counseling groups and behavioral interventions are efficacious. The effects of acupuncture on smoking cessation are not fully elucidated. Prompt smoking cessation or gradual reduction strategies have similar success rates.