Tyrimo darbo tikslas - įvertinti ir palyginti propofolio, ketamino ir jų derinio farmakologinį poveikį eksperimentiniame izoliuotų aortos ir trachėjos žiedų modelyje in vitro. Bandymui atlikti naudojama vienos kameros organų vonelė. Rezultatai fiksuojami programine įranga LabChart 7. Pasirinkti laboratoriniai gyvūnai – 6 Jūrų kiaulyčių patinėliai. Vaistų poveikis vertinimas izoliuotiems aortos ir trahėjos segmentams. Segmentų kontrakcija sukeliama Krebso tirpalu, kuriame yra ištirpintas KCl (80 mmol/l). Pasiekus maksimalų susitraukimą, kumuliuojančiomis koncentracijomis (10-5 M, 10-4 M, 10-3 M), į vonelę pilamas ketamino, propofolio ir jų derinio tirpalas ir kiekvienu atveju fiksuojamas jėgos pokytis. Ketaminas aortos žiedą atpalaiduoja esant didelėms (10-3 M) ir vidutinėms (10-4 M) koncentracijoms, o propofolis ir ketamino/propofolio derinys tik esant didelėms koncentracijoms (p<0,05). Ketaminas, propofolis ir jų derinys atpalaiduoja trachėjos žiedą esant vidutinėms ir didelėms koncentracijoms (p<0,05). Ketamino vidutinė koncentracija turi didesnį poveikį aortos, o vidutinė ir didelė koncentracija – trachėjos žiedo atsipalaidavimui nei propofolis (p<0,05). Ketamino/propofolio derinys santykiu 1:1 esant 10-4 M koncentracijai mažiau veikia aortos atsipalaidavimą nei ketaminas (p<0,05), o 10-4 M ir 10-3 M derinio koncentracijos mažiau veikia trachėjos atsipalaidavimą nei vartojant ketaminą ir propofolį ne derinyje (p<0,05). Didėjant vaistų koncentracijai, didėja jų dilatacinis... [toliau žr. visą tekstą] / The aim of the study was to investigate and compare propofol, ketamine and ketamine/propofol combination pharmacological effects of isolated aortic and tracheal rings in vitro. Single-chamber organ bath was used for the experiment. The results were recorded by LabChart software. Selected laboratory animals – 6 guinea pig males. The influence of medicine over isolated aorta and trachea rings was evaluated. Pre-contraction was induced by Krebs solution containing dissolved KCl (80 mmol/l). After reaching the maximum contraction of the preparation, propofol, ketamine and ketamine/propofol mixture solution was separately added to the bath in a cumulative concentrations (10-5 M, 10-4 M, 10-3 M) and in each case the force change was recorded. Ketamine relaxed aortic rings at medium and large concentrations, while propofol and ketamine/propofol mixtures only in large concentrations (p<0,05). Medium concentration of ketamine showed a greater effect on aortic rings than propofol and medium and large concentrations showed a greater effect on trachea ring than equal concentration of propofol (p<0,05). An average concentration of a 1:1 ratio of ketamine/propofol mixture, had a lower impact on aortic ring relaxation than an equal concentration of ketamine (p <0.05). A high concentration of 1:1 ratio of ketamine/propofol had a lower impact on the trachea ring relaxation than equal concentration of ketamine and propofol used separately (p <0.05). In conclusion, contractions of aorta and... [to full text]

BACKGROUND: Operation Giving Back (OGB) of the American College of Surgeons (ACS) and various other surgical missions in the developing world have become more popular and provide a valuable way of reducing the surgical burden worldwide. While most cases are "bread and butter" general surgery, difficult surgeries are often encountered. MATERIALS AND METHODS: Description of a total thyroidectomy for super giant goiter extending to chest inferiorly, lateral neck and behind both ears, compressing the trachea and causing chronic difficulties breathing. The surgical team was unable to intubate, but performed surgery under local anesthesia and sedation with Ketamine injection. RESULTS: Total thyroidectomy, as a life-saving procedure, was performed under local anesthesia and Ketamine with mild sedation. Once thyroid was removed, the outside diameter of trachea was assessed to be 4mm. Patient tolerated the procedure well and had no postoperative complication. Her breathing improved significantly post-operatively. Five years later, she is doing well. CONCLUSION: Total thyroidectomy for giant goiters can be done under local anesthesia with Ketamine and proper sedation. Surgeons and anesthesiologists participating in surgical missions may have to perform major surgery under local anesthesia. (C) 2015 The Authors. Published by Elsevier Ltd. on behalf of Surgical Associates Ltd.

A 41-year-old woman presented with burning and erythema in her extremities triggered by warmth and activity, which was relieved by applying ice. Extensive workup was consistent with adult-onset primary erythromelalgia (EM). Several pharmacological treatments were tried including local anesthetics, capsaicin, ziconotide, and dantrolene, all providing 24-48 hours of relief followed by symptom flare. Interventional therapies, including peripheral and sympathetic ganglion blocks, also failed. Thus far, clonidine and ketamine have been the only effective agents for our patient. Genetic testing was negative for an EM-associated mutation in the SCN9A gene, encoding the Na(V)1.7 sodium channel, suggesting a mutation in an alternate gene.

Purpose: The purpose of this study was to create an experimental design to compare the regimen of ketamine-midazolam to chloral hydrate-meperidine-hydroxyzine for moderate oral conscious sedation. Methods: Patients between 36 and 83 months of age have been randomly assigned to receive 1 of the 2 regimens. Dosages, times, and vital signs will be recorded. Procedures will be recorded on video for assessment of sedation level and behavior. Patients will be contacted to evaluate postoperative sleeping, discomfort, and amnesia. Data will be analyzed using two-group t-tests (TOST) of equivalence in means to compare the two groups across the study period. Results: Patient enrollment of the study has begun. In order not to break the blind randomized code, future data analysis is pending final data collection. Conclusions: This study will assist clinicians by establishing if a regimen of ketamine-midazolam is a comparable alternative to a regimen of chloral hydrate-meperidine-hydroxyzine for sedations.

Ketamine has shown promise as a novel treatment for depression and as a means to investigate the biology of depression. The drug effectively and rapidly treats depressed patients with the effects lasting approximately 1 week. However, concerns about ketamine’s efficacy do exist because of the inadequacy of blinding procedures used in existing trials. A dose of 0.5 mg/kg has been found to be most effective. Prolonged ketamine infusions have not extended the antidepressant effect beyond the timeframe of a regular infusion. Repeat infusions may be successful in extending ketamine’s effect, but definite conclusions cannot yet be made in this regard. Combination treatment with escitalopram and cognitive behavioral therapy (CBT) hold promise, as does the development of an intranasal formulation. Ketamine has shown additional efficacy as an acute anti-suicide treatment. Side effects from a single administration usually fade within a few hours and commonly include dissociation, elevations of blood pressure, nausea, and anxiety. Less data is available on the side effects caused by repeated ketamine infusions. Concerns exist regarding genitourinary, hepatic, and cognitive side effects after repeated infusions, as well as a risk of addiction. Research on ketamine’s mechanism of action has focused on the glutamate system in the brain. Ketamine may act by inhibiting release of γ–aminobutyric acid (GABA) from interneurons, activating intrasynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), increasing mammalian target of rapamycin complex 1 (mTORC1) and extracellular signal-regulated kinase (ERK) signaling, enhancing brain-derived neurotrophic factor (BDNF) production, inhibiting glycogen synthase kinase 3 (GSK3), blocking extrasynaptic N-Methyl-D-aspartate receptors (NMDARs), and promoting synaptogenesis and neuroplasticity. The two existing ketamine stereoisomers, (R)- versus (S)-ketamine, have different actions and potentially different efficacies and side effect profiles. Ketamine also produces regional changes in brain activity and connectivity. These include decreased burst firing in the lateral habenula (LHb), increased activity in the prefrontal cortex (PFC) and subgenual anterior cingulate cortex (ACC), and alterations in the amygdala’s response to angry and happy faces. Ketamine has the potential to be developed into a novel and useful clinical tool in the treatment of depression and to advance the understanding of the biology of depression.

Originalmente da Bahia, a espécie Leontopithecus chrysomelas foi introduzida no estado do Rio de Janeiro provavelmente por meio do tráfico e atualmente é encontrado em uma das áreas remanescentes de ocupação natural do mico-leão-dourado (Leontopithecus rosalia) podendo comprometer a sobrevivência do último. Visando mitigar esse problema foi criado um plano de ação, onde se recomenda a captura dos animais introduzidos. Procedimentos de captura e contenção química produzem estresse e afetam diretamente a homeostase, podendo alterar diretamente a saúde e o bem estar dos animais somando-se o fato de os protocolos de capturas atuais gerarem um período de recuperação prolongado. O objetivo deste trabalho consistiu em determinar e comparar os efeitos cardiorrespiratórios da dexmedetomidina, quando associada à cetamina S(+) ou à cetamina racêmica, e do midazolam associado à cetamina S(+), por via intramuscular, na contenção química de mico-leão-da-cara-dourada. Foram utilizados 45 animais da espécie Leontopithecus chrysomelas, adultos, machos, pesando em média 532 gramas, oriundos do Centro de Primatologia do Rio de Janeiro, em parceria com a ONG PRI-MATAS. Os animais foram distribuídos em três grupos onde receberam aleatoriamente as associações: CSM - cetamina S(+) (15 mg/kg) e midazolam (0,5 mg/kg); CSD - cetamina S(+) (15 mg/kg) e dexmedetomidina (10 &micro;g/kg); e CD - cetamina racêmica (15 mg/kg) e dexmedetomidina (10 &micro;g/kg). Foram avaliados os períodos de latência, hábil e de recuperação. A frequência e ritmo cardíacos, frequência respiratória, saturação da oxihemoglobina periférica, pressão arterial sistólica, temperatura retal, qualidade de indução e de recuperação, sedação, antinocicepção e grau de relaxamento muscular foram monitorados a cada cinco minutos durante 50 minutos. Os dados paramétricos foram avaliados pela análise de variância (ANOVA) seguida do teste de Tukey. Os dados não paramétricos foram avaliados pelo teste de Kruskal-Wallis seguido do teste de Dunn para identificar quais grupos apresentavam diferença estatística significativa. O grau de significância estabelecido para as análises foi de 5% (p&lt;0,05). Os valores referentes aos parâmetros de frequência respiratória, saturação da oxihemoglobina periférica, temperatura, pressão arterial sistólica, início da perda de tônus muscular, latência e os períodos de recuperação parcial e total não apresentaram diferença entre os grupos. Já os valores de frequência cardíaca, relaxamento muscular, antinocicepção, grau de sedação e consumo de lidocaína apresentaram diferença significativa entre os mesmos momentos dos grupos CSM e CSD, e CSM e CD. Conclui-se que as associações de dexmedetomidina com cetamina racêmica e cetamina S(+) apresentaram os melhores índices de relaxamento muscular, sedação e antinocicepção e mostraram-se seguras para a realização de cirurgia de vasectomia em micos-leão-da-cara-dourada. Apesar dos grupos CSD e CD apresentarem bradicardia mais acentuada, os valores mantiveram-se dentro do limite esperado. / The Golden-headed lion tamarin, originally endemic to the southern Bahia region, was introduced in the state of Rio de Janeiro probably by illegal wildlife trade activity. The species is currently found in one of the remaining areas of natural occupation of the golden lion tamarin (Leontopithecus rosalia), which may compromise the survival of the latter. In order to mitigate this problem, an action plan was elaborated and the capture of golden-headed lion tamarins recommended. Both capture and chemical restraint procedures can cause stress and compromise homeostasis with a direct effect on the health and well-being of the animals. Besides that, current chemical immobilization protocols usually result in prolonged recovery times. This study aims to determine and compare the cardiovascular and respiratory effects of three different protocols for chemical immobilization of golden-headed lion tamarins. Thirty-five adult male specimens of Leontopithecus chrysomelas were studied. Animals were randomly separated into three groups: ketamine S(+) and midazolam (15 mg kg-1 and 0.5 mg kg--1-) (KSM group), ketamine S(+) and dexmedetomidine (15 mg kg--1- and 10 &micro;g kg-1) (KSD group) and racemic ketamine and dexmedetomidine (15 mg kg-1 and 10 &micro;g kg-1 ) (KD group). Periods of latency, immobilization and recovery were evaluated. Heart rate and rhythm, respiratory rate, peripheral oxyhemoglobin saturation, systolic blood pressure, rectal temperature, induction and recovery quality, sedation, antinociception, and degree of muscle relaxation were monitored every five minutes for 50 minutes. Parametric data were analyzed by using repeated measures analysis of variance (ANOVA) followed by a Tukey\'s test. Non-parametric data were analyzed by the Kruskal-Wallis test followed by Dunn\'s test. Values of P&lt; 0.05 were considered statistically significant. No significant differences were found in respiratory rate, peripheral oxygen saturation, temperature, systolic blood pressure, onset of muscle tone loss, latency and partial and total recovery periods. Heart rate, sedation and muscle relaxation degrees, antinociception, and lidocaine consumption presented significant difference at the same moments between KSM and KSD and between KSM and KD. Marked bradycardia was presented on KSD and KD groups, with values remaining within the normal range. This study demonstrated that combinations of dexmedetomidine with racemic ketamine and S(+) ketamine presents the best outcomes for muscle relaxation, sedation and antinociception and were safe for vasectomy surgery in golden-headed lion tamarins.

A pré-medicação apesar de ser freqüentemente utilizada nos mamíferos, é raramente utilizada nas espécies aviárias. O objetivo deste estudo foi avaliar o efeito da pré-medicação na indução e anestesia com sevofluorano em papagaios. Foram utilizados trinta e seis animais adultos oriundos do Parque ecológico do Tietê. Os animais foram randomicamente distribuídos em três grupos: grupo I (n = 12), tratado com NaCl 0,9% como placebo, grupo II (n = 12), com cetamina 10 mg.Kg-1 e grupo III (n = 12), com cetamina 10 mg.Kg-1 e diazepam 0,5 mg.Kg-1, por via intramuscular. Quinze minutos após a pré-medicação, a indução foi realizada por meio de máscara facial conectada a um circuito sem reinalação, usando 4,5% de sevofluorano em 100% de oxigênio, com um fluxo de 1,5L. Tanto os efeitos cardiovasculares e respiratórios, bem como, a qualidade da pré-medicação, indução e recuperação da anestesia foram avaliadas. A Dose anestésica mínima obtida neste estudo foi de 2.4 &plusmn; 0.37%, 1.7 &plusmn; 0.39%, e 1.3 &plusmn; 0.32% para os grupos I, II e III respectivamente. Foi concluído que a cetamina isolada ou cetamina/diazepam diminuem consideravelmente a dose anestésica mínima em papagaios. A cetamina isolada ou em associação, promoveu uma boa qualidade de sedação, permitindo uma melhor indução da anestesia quando comparada a indução com o agente inalatório. Tanto a cetamina isolada quanto a associação, mostraram-se seguras, não alterando as funções cardiovasculares, a oxigenação ou ventilação, podendo ser utilizados com sucesso nesta espécie. Além disto, a anestesia com o sevofluorano foi considerada segura para esta espécie em todos os protocolos estudados. / Although pre-medication is commonly used in mammals, it is rarely used in avian species. The aim of this study was to evaluate the effect of pre-medication in the induction and anesthesia with sevoflurane in parrots. Thirty-six adults animals were utilized from Tietê ecologic park. The animals were randomically distributed in three groups: group I (n = 12), was pre-medicated with NaCl0.9% as a placebo, group II (n = 12), with ketamine 10 mg.kg-1 and group III (n = 12), with ketamine 10mg.kg-1 and diazepam 0.5mg.kg-1, intramuscularly. Fifteen minutes after pre-medication, the induction was accomplished with a facial mask connected to a non rebreathing circuit using 4.5% of sevoflurane in 100% oxygen with a flow rate of 1.5L. The cardiovascular and respiratory effects were evaluated as well as the quality of pre-medication, induction and recovery of anesthesia. The minimal anesthetic concentration obtained at this study was 2.4 &plusmn; 0.37%, 1.7 &plusmn; 0.39%, and 1.3 &plusmn; 0.32% for group I, II and III respectively. It was concluded that ketamine alone or ketamine/diazepam consider decreased the DAM of sevofluorano in parrots. ketamine alone or in association, promoted a good quality of sedation allowing better induction of anesthesia when compared with the induction with inhalant agent. Even ketamine alone or the association were considered a safe procedure, not changing cardiovascular, oxygenation and ventilation and could be successfully used in this specie. Furthermore, the anesthesia with sevoflurane was considered safe to this specie in all protocols.

Major depressive disorder (MDD) is a growing health problem. Current treatment options are not always effective and take several weeks of regular administration before an improvement can be seen in symptoms. Sub-anaesthetic doses of ketamine have been found to have antidepressant effects in previously treatment-resistant MDD after just one dose. However, ketamine also produces short term psychosis-like side effects which are undesirable for MDD patients. Ketamine is known to be an NMDA receptor antagonist, binding within the channel pore to block ion flow, however the molecular mechanism(s) underlying its antidepressant and psychosis-like effects are still unclear. In this thesis several genetically modified mouse lines were used to probe the molecular events involved in ketamine's actions. Firstly, a mouse line in which the c-terminal domain (CTD) of the NMDAR subtype GluN2B had been replaced with that of GluN2A, and a second line in which the opposite replacement had taken place, were used to investigate the role of the CTD in the NMDAR response to ketamine. It was found that the GluN2B CTD is required for the short-term psychosis-like response to a sub-anaesthetic dose of ketamine. This is interesting as the channel pore region, containing the binding site for ketamine, is unaltered in these mutants. Therefore, this finding implicates GluN2B CTD specific intracellular signalling molecules in this action of ketamine and raises the question of whether the CTD itself is able to respond to ketamine binding within the pore to induce signalling changes, perhaps via a conformational change. Secondly, a mouse line, in which the activity-regulated synaptic protein Arc has been tagged with a fluorescent marker, was used to investigate the response of synapses to both anaesthetic and sub-anaesthetic doses of ketamine. In this experiment tagged Arc protein was visible as punctate accumulations at synapses. A novel method termed 'synaptome mapping' was used to image these accumulations across entire coronal sections and to quantify their number, size and intensity. Using this method alterations to the Arc synaptome map were detected 1h, 6h and 24h following ketamine administration. The two doses used produced different changes to this map, with the sub-anaesthetic antidepressant dose inducing increases in Arc puncta number across many brain regions, whereas the anaesthetic dose induced short term (1h) increases followed by longer term decreases in Arc puncta number. This finding links long-term increases in Arc at the synapse with an antidepressant response to ketamine.

Benzodiazepines (Benzos) and ketamine (K) are compounds that have been encountered in Drug-Facilitated Sexual Assault (DFSA) cases. Due to the intimate nature of these crimes, evidence collection is often postponed due to delays and/or reluctance in reporting these crimes. Further delays in analysis may be encountered in laboratories with large caseloads and/or backlogs. Drug identification in biological samples is important to determine whether victims knowingly or unknowingly took an impairing substance, however, the results could be negative due to chemical degradation over a long storage period. The purpose of this project was to study if degradation could be prevented with a new preservation method at the time of collection. Urine samples were prepared by the addition of K and metabolites and selected benzos and metabolites that were subjected to different sample pre-treatment techniques, and were analyzed after storage at room temperature (25°C), refrigerator (4°C) and freezer (-20°). The samples were either pre-treated with preservative (0.5% toluene) or filtration sterilization (sterile filter kit) within two hours after sample collection, and a control group with no pre-treatment was incorporated into the study for comparison. The changes in concentrations over 50 days (Benzos group) and 210 days (K group) were evaluated between different pre-treated methods and different temperature conditions. Sample that were treated with 0.5% toluene showed the most degradation: 44% of oxazepam and 96% of diazepam degraded over 10 days, and 80% of dehydronorketamine degraded after storage of 150 days regardless the temperature conditions. Clonazepam and flunitrazepam concentrations were reduced by 80% of the original concentration when stored at room temperature for 10 days. The major benzodiazepines evaluated in this study were stable when stored in the freezer. In K group, ketamine and norketamine that were stored at room temperature and refrigerated over 210 days were stable, however, degradation was observed after 150 days when the samples were stored in the freezer. There was no statistically different change observed among the samples pre-treated with or without filtration sterilization. Each sample pH was measured and it was determined that those stored at room temperature had an average pH of 8.5, while samples stored in the refrigerator and freezer had an average pH of 6.7 and 6.5, respectively. This finding revealed that pH could be the major factor affecting compound degradation rather than the bacterial contamination with high pH contributing to degradation, and low pH potentially preventing sample lost.

Ocular hypertension has been identified as the fundamental risk factor in glaucoma which is the leading cause for irreversible blindness in the world. Understanding the different factors that affect IOP is of utmost importance in clinical management as IOP is considered as the fundamental factor in assessing the efficiency of glaucoma medications. Several studies have attempted to assess factors that could affect IOP including age, body position, blood pressure, anesthetics commonly used during eye operations, etc. However, in most of these studies IOP is measured under anesthesia using rodent models and these anesthetics could affect the IOP measurements directly or indirectly. The use of tonometry in such experiments also includes certain limitations like acquiring IOP at discrete moments in time, human error while handling the instrument and stress induced spikes in IOP while handling awake animals. This study uses a wireless continuously monitoring device to eliminate these limitations while also acquiring IOP at a higher rate. Anesthesia induction is known to lower body temperature. However, previous studies on the effects of various anesthetic agents fail to take into account this drop in body temperature which could potentially lead to erroneous results. This thesis focuses on studying the effects of two commonly used anesthetic agents, isoflurane and ketamine while accounting for loss in body temperature. The effects of changing body temperature on intraocular pressure was also studied to help understand the effects of these factors accurately. There was a statistically significant drop (p<0.001) in intraocular pressure post isoflurane induction with no heat support across several animals. The addition of heat support in the next set of experiments resulted in an almost steady pressure throughout the experiment. Since the body temperature was maintained constant throughout the experiment, there was no statistically significant difference (p>0.05) among IOP’s for the awake and anesthetized condition. This conclusion was then confirmed by obtaining a direct effect of changing body temperature on IOP. There was a rise in IOP while the animal was placed on a 42 degree Celsius heating pad and a drop in IOP while the animal was placed on a 20 degree Celsius surface with no heat support. The corresponding changes in body temperature were confirmed using a rectal thermometer. There were no significant changes in the IOP measured by the sensor while measuring pressure with the iCare tonolab. Applanation tonometry however produced an average mean intraocular pressure increase of 2.11 ± 1.62 mmHg.