Injection Of Ketamine Research Articles

Classical conditioning of antidepressant placebo effects in mice.

Placebo effects in human clinical trials for depression treatment are robust and often comparable to drug effects. Placebo effects are traditionally difficult to study in rodents due to the slow-onset action of classical antidepressant drugs. We hypothesized that the rapid antidepressant actions of ketamine would allow modeling antidepressant placebo effects in rodents. Male and female CD-1 mice received either ketamine or saline injections with concomitant exposure to specific environmental conditioning stimuli, for a total of three drug/conditioning sessions each2weeks apart. Two weeks later, during an evocation phase, mice were exposed to the drug-paired conditioning stimuli or no conditioned stimuli followed by testing for motor stimulatory actions and antidepressant-like effects using the forced swim test. Negative (no ketamine administration at any time) and positive (acute ketamine administration prior to evocation testing) control groups were included as comparators. Both male and female mice exhibited increased locomotor activity following ketamine administration during the conditioning phase, which was not observed following exposure to the conditioning stimuli. Exposure to the conditioning stimuli previously paired with ketamine, similar to an acute ketamine administration, reduced immobility time in the forced swim test both 1 and 24h after administration in male, but not female, mice. These results represent the first evidence of antidepressant-like placebo-conditioned effects in an animal model. The developed approach can be used as a model to explore the neurobiological mechanisms of placebo effects, their possible sexually dimorphic effects, and relevance to mechanisms underlying antidepressant action.

Ketamine Administration Reverses Corticosterone-Induced Alterations in Excitatory and Inhibitory Transmission in the Rat Dorsal Raphe Nucleus

Ketamine, a N-methyl-D-aspartate (NMDA) receptor antagonist, exerts rapid antidepressant effects in human patients and ameliorates depressive-like behavioral effects of chronic stress in animal models. Chronic stress and elevated corticosterone levels have been shown to modify serotonin (5-HT) neurotransmission, and ketamine's antidepressant-like activity involves a 5-HT-dependent mechanism. However, it is not known if and how ketamine affects the electrophysiological characteristics of neurons and synaptic transmission within the dorsal raphe nucleus (DRN), the main source of 5-HT forebrain projections. Our study was aimed at investigating the effects of a single ketamine administration on excitatory and inhibitory transmission in the DRN of rats which had previously been administered corticosterone twice daily for 7 days. Spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) were then recorded from DRN projection cells in ex vivo slice preparations obtained 24 h after ketamine injection. Repeated corticosterone administration increased sEPSC frequency and decreased sIPSC frequency in DRN projection cells. There were no changes either in the amplitude of postsynaptic currents or in the excitability of these cells. In slices prepared from rats with ketamine administered after the end of corticosterone treatment, the frequencies of sEPSCs and sIPSCs were similar to those in control preparations. These data indicate that a single administration of ketamine reversed the effects of corticosterone on excitatory and inhibitory transmission in the DRN.

Increased Reactivity of the Mesolimbic Reward System after Ketamine Injection in Patients with Treatment-resistant Major Depressive Disorder.

The antidepressant effect of ketamine is associated with increased activity in the reward circuitry of the brain and a suppression of circuitry that mediates perceptual processing of negative emotions. The duration of ketamine effect on these brain structures remains to be defined. As expected, ketamine administration led to an improvement in mood and global vigilance. The improvement in mood was accompanied by an increased recruitment of the orbitofrontal cortex, ventral striatum, medial substantial nigra and ventral tegmental area, structures that are part of the reward circuitry.Responses in the mesolimbic structures (amygdala, medial substantial nigra and ventral tegmental area, orbitofrontal cortex) to negative stimuli were decreased after ketamine administration.The data are consistent with the premise that ketamine induces sustained changes in the mesolimbic neural circuits to reset pathological reward and emotional processing. Ketamine rapidly improves maladaptive mood states in major depressive disorder, and some of the neural substrates underlying this therapeutic effect have been identified. This study aimed to identify functional changes within neural networks that may underlie the impact of ketamine on both reward and emotional processing in patients with treatment-resistant major depression. Ten adult patients with a Montgomery-Åsberg Depression Rating Scale score above 25 were enrolled to receive a single intravenous administration of ketamine (0.5 mg/kg). Patients' performance along with related neural network activations were analyzed in a game-like reward task and in an emotional judgment task using functional magnetic resonance imaging 1 day before and 1 and 7 days after ketamine administration. A significant correlation (R = 0.46, P = 0.03) between the improvement of depression scores and the enhanced reaction time for positive items was found in the game-like reward task 1 day after ketamine administration. This enhanced sensitivity for rewarded items was accompanied by increased activity of reward-related brain regions, including the orbitofrontal cortex, ventral striatum, and the ventral tegmental area, an effect that persisted up to 1 week after ketamine injection. In the emotional judgment task, it was found that ketamine rapidly modified local brain activities in response to emotionally negative, positive, or neutral stimuli in the amygdala, insula, anterior cingulate cortex, and in the ventral tegmental area. Single bolus ketamine administration rapidly triggers lasting changes in mesolimbic neural networks to improve pathologic reward and emotional processing in patients with major depressive disorder.

Effects of Pre-treatment with Ketamine and Tourniquet Application on the Prevention of the Pain Induced by Propofol Injection: A Randomized Controlled Clinical Trial

Introduction: The pain induced by propofol injection is a common adverse complications caused by propofol, which is ranked seventh among the 33 clinical symptoms of anesthesia. The present study aimed to investigate the effects of pre-treatment with ketamine and tourniquet inflation on the pain induced by propofol injection.Methods: This randomized controlled clinical trial was conducted on 120 patients with the American Society of Anesthesiologists (ASA) physical status classification I. The patients were assigned to six groups. In groups one and four, tourniquet was inflated above the angiocatheter. In groups two and five, ketamine was injected 30 seconds before propofol injection with no tourniquet. The patients in groups three and six were injected with propofol alone. To assess the severity of pain, verbal rating scores were used. Data analysis was performed in SPSS version 20.Results: In total, 74 male and 46 female patients were examined. In terms of pain severity, the lowest level of pain was experienced with the injection of ketamine before propofol with the use of a tourniquet (groups one and four). Based on the injection site, the total pain scores were higher with the injection of propofol into the veins on the dorsum of the hand. In addition, the mean pain score in groups one, two, four, and five was significantly lower compared to groups three and six (P< 0.05)Conclusion: According to the results, use of ketamine, especially with a tourniquet, could alleviate the pain induced by propofol injection.

Breathing under Anesthesia: A Key Role for the Retrotrapezoid Nucleus Revealed by Conditional Phox2b Mutant Mice.

Optimal management of anesthesia-induced respiratory depression requires identification of the neural pathways that are most effective in maintaining breathing during anesthesia. Lesion studies point to the brainstem retrotrapezoid nucleus. We therefore examined the respiratory effects of common anesthetic/analgesic agents in mice with selective genetic loss of retrotrapezoid nucleus neurons (Phox2b mice, hereafter designated "mutants"). All mice received intraperitoneal ketamine doses ranging from 100 mg/kg at postnatal day (P) 8 to 250 mg/kg at P60 to P62. Anesthesia effects in P8 and P14 to P16 mice were then analyzed by administering propofol (100 and 150 mg/kg at P8 and P14 to P16, respectively) and fentanyl at an anesthetic dose (1 mg/kg at P8 and P14 to P16). Most mutant mice died of respiratory arrest within 13 min of ketamine injection at P8 (12 of 13, 92% vs. 0 of 8, 0% wild type; Fisher exact test, P < 0.001) and P14 to P16 (32 of 42, 76% vs. 0 of 59, 0% wild type; P < 0.001). Cardiac activity continued after terminal apnea, and mortality was prevented by mechanical ventilation, supporting respiratory arrest as the cause of death in the mutants. Ketamine-induced mortality in mutants compared to wild types was confirmed at P29 to P31 (24 of 36, 67% vs. 9 of 45, 20%; P < 0.001) and P60 to P62 (8 of 19, 42% vs. 0 of 12, 0%; P = 0.011). Anesthesia-induced mortality in mutants compared to wild types was also observed with propofol at P8 (7 of 7, 100% vs. 0 of 17,7/7, 100% vs. 0/17, 0%; P < 0.001) and P14 to P16 (8 of 10, 80% vs. 0 of 10, 0%; P < 0.001) and with fentanyl at P8 (15 of 16, 94% vs. 0 of 13, 0%; P < 0.001) and P14 to P16 (5 of 7, 71% vs. 0 of 11, 0%; P = 0.002). Ketamine, propofol, and fentanyl caused death by respiratory arrest in most mice with selective loss of retrotrapezoid nucleus neurons, in doses that were safe in their wild type littermates. The retrotrapezoid nucleus is critical to sustain breathing during deep anesthesia and may prove to be a pharmacologic target for this purpose.

Comparison of the Efficacy and Side Effects of Intravenous and Intramuscular Injection of Ketamine for Children Requiring Sedation: A Randomized Double-Blind Clinical Trial Study

Background Ketamine is an antagonist receptor of N-methyl-D-aspartate (NMDA), and phencyclidine derivate sedative agent. Thus the aim of this study was to evaluate the effect of intravenous (IV) and intramuscular (IM) injection of Ketamine for sedation procedure of children. Materials and Methods In this randomized clinical trial the patients, 1-6 year-old children referred to Emergency Department of Ahvaz Golestan and Imam Khomeini Hospitals, Ahvaz city, Iran, were divided randomly into two groups (IV and IM groups). Patients in the IV group received ketamine with dose of 1.5 mg/kg intravenously and the patients in the IM group received ketamine with dose of 4 mg/kg intramuscularly. Then efficacy and side effects in both groups were performed every 5 minutes for the first for the first 15 minutes. Results 222 patients with indication for sedation were enrolled. Results showed that in 1st min, most of the patients that received IM ketamine were in level 1 of sedation (67.6 %, n= 73); while the majority of patients that received IV ketamine were in level 1 to 3 of sedation (28.9%, 24.6% and 26.3%, respectively) (P<0.001). Moreover, in 5th min, most of the patients that received IV ketamine were in level 6 of sedation (62.3%), while those who received IM ketamine were in level 5 of sedation (52.8%) (P<0.001), which was better in IV group. While in 15th min, we did not find significant differences between the groups (P=0.057). Conclusion The results of this study showed the beneficial effects of IV ketamine in making better sedation levels in pediatric patients for different purpose (medical and para-clinical procedures).

General Anesthesia Does Not Have Persistent Effects on Attention in Rodents.

Background: Studies in animals have shown that general anesthesia can cause persistent spatial memory impairment, but the influence of anesthetics on other cognitive functions is unclear. This study tested whether exposure to general anesthesia without surgery caused a persistent deficit in attention in rodents.Methods: To evaluate whether anesthesia has persistent effects on attention, rats were randomized to three groups. Group A was exposed for 2 h to isoflurane anesthesia, and tested the following seven days for attentional deficits. Group B was used as a control and received room air before attentional testing. Since there is some evidence that a subanesthetic dose of ketamine can improve cognition and reduce disorders of attention after surgery, rats in group C were exposed to isoflurane anesthesia in combination with a ketamine injection before cognitive assessment. Attention was measured in rats using the 5-Choice Serial Reaction Time Task, for which animals were trained to respond with a nose poke on a touchscreen to a brief, unpredictable visual stimulus in one of five possible grid locations to receive a food reward. Attention was analyzed as % accuracy, % omission, and premature responses.Results: Evaluating acute attention by comparing baseline values with data from the day after intervention did not reveal any differences in attentional measurements. No significant differences were seen in % accuracy, % omission, and premature responses for the three groups tested for 7 consecutive days.Conclusion: These data in healthy rodents suggest that general anesthesia without surgery has no persistent effect on attention and the addition of ketamine does not alter the outcome.

Prophylactic Ketamine Treatment Promotes Resilience to Chronic Stress and Accelerates Recovery: Correlation with Changes in Synaptic Plasticity in the CA3 Subregion of the Hippocampus.

Ketamine is an N-methyl-d-aspartate receptor antagonist that has gained wide attention as a potent antidepressant. It has also been recently reported to have prophylactic effects in animal models of depression and anxiety. Alterations of neuroplasticity in different brain regions; such as the hippocampus; prefrontal cortex; and amygdala; are a hallmark of stress-related disorders; and such changes may endure beyond the treatment of symptoms. The present study investigated whether a prophylactic injection of ketamine has effects on structural plasticity in the brain in mice that are subjected to chronic unpredictable stress followed by an 8-day recovery period. Ketamine administration (3 mg/kg body weight) 1 h before stress exposure increased the number of resilient animals immediately after the cessation of stress exposure and positively influenced the recovery of susceptible animals to hedonic deficits. At the end of the recovery period; ketamine-treated animals exhibited significant differences in dendritic spine density and dendritic spine morphology in brain regions associated with depression compared with saline-treated animals. These results confirm previous findings of the prophylactic effects of ketamine and provide further evidence of an association between the antidepressant-like effect of ketamine and alterations of structural plasticity in the brain

The arousal effect of hyperbaric oxygen through orexin/hypocretin an upregulation on ketamine/ethanol-induced unconsciousness in male rats.

Approaches that facilitate the recovery from coma would have enormous impacts on patient outcomes and medical economics. Orexin-producing neurons release orexins (also known as hypocretins) energy-dependently to maintain arousal. Hyperbaric oxygen (HBO) could increase ATP levels by preserving mitochondrial function. We investigated, for the first time, the arousal effects of HBO and orexins mechanisms in a rat model of unconsciousness induced by ketamine or ethanol. A total of 120 Sprague-Dawley male rats were used in this study. Unconsciousness was induced either by intraperitoneal injection of ketamine or ethanol. The HBO treatment (100% O2 at 3 ATA) was administered immediately after unconsciousness induction for 1hr. SB334867, orexin-1 receptor (OX1R) inhibitor, or JNJ10397049, orexin-2 receptor (OX2R) inhibitor was administered 30min intraperitoneally before unconsciousness induction. Loss of righting reflex test (LORR) and Garcia test were used to evaluate the unconsciousness duration and neurological deficits after recovering from unconsciousness, respectively. Enzyme-linked immunosorbent assay was used to measure brain tissue ATP and orexin A levels. Ketamine or ethanol injection resulted in LORR immediately and neurological deficits 6hr after unconsciousness induction. HBO treatment significantly reduced the LORR duration, improved Garcia scores and unregulated ATP and orexin A levels in the brain tissue. Administration of OX1R inhibitor or OX2 R inhibitor abolished arousal and neurological benefits of HBO. In conclusion, HBO exerted arousal-promoting effects on unconscious rats induced by ketamine orethanol. The underlying mechanism wasvia, at least in part, ATP/orexin A upregulation. HBO may be a practical clinical approach to accelerate unconsciousness recovery in patients.

Prelimbic neuronal nitric oxide synthase inhibition exerts antidepressant-like effects independently of BDNF signalling cascades.

NMDA antagonists and nitric oxide synthase (NOS) inhibitors induce antidepressant-like effects and may represent treatment options for depression. The behavioural effects of NMDA antagonists seem to depend on Tyrosine kinase B receptor (TrkB) activation by BDNF and on mechanistic target of rapamycin (mTOR), in the medial prefrontal cortex (mPFC). However, it is unknown whether similar mechanisms are involved in the behavioural effects of NOS inhibitors. Therefore, this work aimed at determining the role of TrkB and mTOR signalling in the prelimbic area of the ventral mPFC (vmPFC-PL) in the antidepressant-like effect of NOS inhibitors. Pharmacological treatment with LY235959 or ketamine (NMDA antagonists), NPA or 7-NI (NOS inhibitors), BDNF, K252a (Trk antagonist) and rapamycin (mTOR inhibitor) injected systemically or into vmPFC-PL followed by behavioural assessment. We found that bilateral injection of BDNF into the vmPFC-PL induced an antidepressant-like effect, which was blocked by pretreatment with K252a and rapamycin. Microinjection of LY 235959 into the vmPFC-PL induced antidepressant-like effect that was suppressed by local rapamycin but not by K252a pretreatment. Microinjection of NPA induced an antidepressant-like effect insensitive to both K252a and rapamycin. Similarly, the antidepressant-like effects of a systemic injection of ketamine or 7-NI were not affected by blockade of mTOR or Trk receptors in the vmPFC-PL. Our data support the hypothesis that NMDA blockade induces an antidepressant-like effect that requires mTOR but not Trk signalling into the vmPFC-PL. The antidepressant-like effect induced by local NOS inhibition is independent on both Trk and mTOR signalling in the vmPFC-PL.

Transition from status epilepticus to interictal spiking in a rodent model of mesial temporal epilepsy

Status epilepticus (SE) is a serious, life-threatening condition requiring immediate care to prevent neuronal injury and long-term functional deficits. SE is modeled in rodents by systemic injection of chemoconvulsants such as pilocarpine, which induces EEG and behavioral activities similar to what seen in humans. Combined injection of diazepam and ketamine is commonly used to terminate SE in rodents but, to date, no study has analysed the EEG activity and behavior during SE and after diazepam + ketamine administration. We therefore performed EEG recordings from the hippocampal CA3 region of mice before and during pilocarpine-induced SE as well as for 24 h after injection of diazepam + ketamine. We found that although convulsive behavior disappeared within 5.5 min ( ± 1.12 min; n = 5) after diazepam + ketamine treatment, EEG epileptiform activity resembling what seen during SE persisted up to 278.8 min ( ± 262.0 min). The end of this SE-like EEG pattern was characterised by transition to high amplitude, persisting interictal spikes. Our findings show that (i) administration of diazepam and ketamine stops behavioral but not EEG epileptiform activity associated to pilocarpine-induced SE; and (ii) such SE-like EEG pattern persists for approx. 4 h to be replaced by interictal spikes that predominate during the so called latent period in this model of mesial temporal lobe epilepsy.

Morin decreases cortical pyramidal neuron degeneration via inhibition of neuroinflammation in mouse model of schizophrenia

Neuroinflammation plays a prominent role in the pathophysiology and progression of schizophrenia. Thus, suppression of neuroinflammation may retard the progression of the disease. This study was designed to investigate whether morin, a bioactive compound with antipsychotic-like activity could reduce biomarkers of neuroinflammation and neurodegeneration in lipopolysaccharide (LPS)- and ketamine (KET)-induced schizophrenic-like behavior in mice. Animals were treated once daily intraperitoneally with morin (100 mg/kg), haloperidol (1 mg/kg), risperidone (0.5 mg/kg), or saline (10 mL/kg) in combination with LPS (0.1 mg/kg) for 14 consecutive days. However, from days 8–14, overt schizophrenia-like episode was produced with i.p. injection of KET (20 mg/kg) once daily. Schizophrenic-like behaviors: positive (open-field test), negative (social-interaction and social-memory tests) and cognitive (Y-maze test) symptoms were assessed on day 14. Thereafter, the levels and expressions of biomarkers of neuroinflammation were estimated in the striatum (ST), prefrontal cortex (PFC) and hippocampus (HC) using spectrophotometry, ELISA and immunohistochemistry. The effects of morin on cortical pyramidal neurons were estimated using Golgi-impregnation staining technique. LPS in combination with KET significantly (p < 0.05) induced schizophrenia-like behaviors, which was attenuated by morin. Morin significantly (p < 0.05) decreased tumor necrosis factor-α, interleukine-6 levels and myeloperoxidase activity in the ST, PFC and HC of mice treated with LPS + KET. Moreover, morin reduced regional brain expressions of cyclooxygenase-2, inducible nitric oxide synthase and nuclear factor kappa-B, and also rescued loss of pyramidal neurons in the PFC. Taken together, these findings suggest that morin reduces schizophrenic-like symptoms induced by LPS + KET via mechanisms related to inhibition of the release of pro-inflammatory mediators and suppression of degeneration of cortical pyramidal neurons in mice.

Intusussception Secondary to Gastrointestinal Foreign Body in an Eleven Month old Juvenile African Lion (Panthera Leo) Case Report

Abstract An eleven month old male, juvenile lion brought for rehabilitation at the Olusegun Obasanjo Presidential Library (OOPL) Wildlife Park was diagnosed with gastrointestinal foreign body and intussusception based on the history of persistent vomiting following ingestion of a cotton towel, and radiographic findings of a radiopaque gastric foreign body extending from the fundus to the pylorus and a cylindrical soft tissue mid-abdominal mass. The lion was premedicated with an intramuscular injections of ketamine (5 mg.kg−1) and midazolam (0.25 mg.kg−1), while anaesthesia was induced with an intravenous injection of propofol (2 mg.kg−1). A celiotomy followed by gastrotomy and subsequent intestinal resection and anastomosis was performed to remove the gastrointestinal foreign bodies and correct the intussus ception. The lion recovered well without any complication and was gradually introduced back into the group housing three weeks later following successful alimentation process. This report is probably the first case of intussusception in a lion that was associated with a gastrointestinal foreign body.

Ketamine-induced antidepressant like effects in mice: A possible involvement of cannabinoid system

The purpose of this study was to explore the possible interaction between ketamine and cannabinoid system in the modulation of depression-related responses using the forced swimming test (FST), tail suspension test (TST) and open-field test (OFT) in mice. Our results revealed that intra-peritoneal (i.p.) injection of ketamine (5 and 10 mg/kg), a non-competitive NMDA antagonist, dose-dependently produced antidepressant-like effect in the FST. Moreover, i.p. administration of both CB1 and CB2 receptor drugs: ACPA (1 mg/kg; CB1 receptor agonist), AM251 (1 mg/kg; CB1 receptor antagonist), GP1a (2 mg/kg; CB2 receptor agonist) and AM630 (0.5 mg/kg; CB2 receptor antagonist) exhibited antidepressant action. Interestingly, the concomitant administration of ineffective doses of ketamine and cannabinoid receptor antagonists provoked the antidepressant-like effects as compared to control group. It should be considered, all above mentioned doses of drugs could not change locomotor activity in the OFT. It seems that possible interaction between ketamine and cannabinoid system may modulate depression-related behavior.

Ketamine Tolerance in Sprague-Dawley Rats after Chronic Administration of Ketamine, Morphine, or Cocaine.

Ketamine is one of the most commonly used anesthetics in human and veterinary medicine, but its clinical effectiveness is often compromised due to tolerance to its anesthetic effects. Although ketamine tolerance has been demonstrated in a number of behavioral measures, no published work has investigated tolerance to ketamine's anesthetic effects other than duration of anesthesia. In addition, a reported practice in anesthesiology is to alter anesthetic doses for procedures when the patient has a history of drug abuse. Empirically investigating the effects of administration of a drug of abuse on ketamine's potency and efficacy to produce anesthesia could help in the creation of anesthetic plans that maximize safety for both clinicians and patients. The goal of the current study was to test the effects of repeated administration of ketamine, morphine, or cocaine on ketamine's ability to produce anesthesia. In 2 studies, male Sprague-Dawley rats received daily injections of ketamine (32 or 100 mg/kg IP), morphine (3.2 or 5.6 mg/kg IP), or cocaine (3.2 or 10 mg/kg IP) for 14 consecutive days and then were tested on day 15 for ketamine-induced anesthesia by using a cumulative-dosing procedure (32 to 320 mg/kg IP). Chronic treatment with either ketamine or morphine-but not cocaine-produced tolerance to ketamine's anesthetic effects in a dose-dependent manner. These results suggest that ketamine's clinical effectiveness as an anesthetic will vary as a function of its history of use. Furthermore, given that chronic morphine administration produced tolerance to ketamine's anesthetic effects, various pain medications may reduce ketamine's effectiveness for anesthesia.

Clinical and experimental Study to evaluate the effect of Biphasic calcium phosphate collagen composite (cpcc) on healing of bone defects after oral surgical procedures

Background: A recent discoveries used for reconstruction in maxillofacial surgery is the composite bone graft materials. The availability of collagen I matrix make our choice to use this material in surgery .It is biomaterials that its structure could be modified by simple techniques. Studies to find a new materials use for bone reconstruction is to overcome the disadvantages of autogenous bone and the synthetic resorbable bone substitutes.&#x0D; Objectives: This study was done to evaluate the effect of biphasic calcium phosphate collagen composite (ccpc) on healing of bone defects after oral surgical procedures.&#x0D; Type of the study: A cross sectional study.&#x0D; Method: It involved 60 patients, 35 male and 25 female, age (15-40) yearsand experimental animals study involved sixty rabbits.The study was done in Department of Maxillofacial surgery in Al anbarCollege of Dentistry (2015-2016).These patients were received tooth extraction, and other minor surgical procedures .Clinical and radiographical examination and patients consents are done before surgery. The surgery was done under local anesthesia.The resulting bone cavities are filled with composite bone graft material composed from combination of lyophilized hydrolysed collagen sponge (Hemospon),Brasil and Osteon II bone graft material,Korea .The area is closed with 3/0 block silk suture .Antibiotic cover (Ampicillin 500mg ×4) for 1 week was prescribed. The patients were followed up by careful clinical examination with radiograph 15-30 days after surgery. .Sixty New Zeleandi White rabbit were used in our study for histopathologicalexamination.Intraperitoneal injection of ketamine 10 mg with XYL-M2 solution 20 mg xylazine base used to anesthetize the animals. (5mm diameter) bone defects were made using straight surgical hand piece and bur in anterior mandibular region and filled with each material. The study design involve the following groups: group 1( involve 15 rabbit; the defect was made and filled with blood clot only (control group),group 2( involve 15 rabbit, the defect was made and filled with collagen sponge only),group 3(Involve 15 rabbit, the defect was made and filled with Osteon II bone graft only),group4( involve 15 rabbit, the defect was made and filled with Osteon II bone graft +collagen (Composite bone graft).The flap were closed 3/0 black silk suture. The rabbits were killed after 30 days. 10 cmexcisional biopsy specimen was taken from the paramandibular area and placed in 10%formalin then send histopathologicalexamination.&#x0D; Results: Clinically, the treated area show good healing with absence of infection .Radiographs during follow up period show radiopacity indicating new bone formation .The results of experimental animals (Rabbits) indicategrowth new bone . In group 1 and group2, the center of the defects was depressed by surrounding tissues Eung et al, While, in group 3&amp;group 4, the graft materials maintained the space and the center of the defect did not depress. Statistical analysis indicates that during 4 th week ,the highest healing % is (100%) in group 3 &amp;group4 in compared to control group (50%)..A significant difference in healing % was found among the treated groups.&#x0D; Conclusion:The result indicates that biphasic calcium phosphate collagen composite can be efficiently utilized clinically.

Smad3 Suppresses Epithelial Cell Migration and Proliferation via the Clock Gene Dec1, Which Negatively Regulates the Expression of Clock Genes Dec2 and Per1

Smad3 has circadian expression; however, whether Smad3 affects the expression of clock genes is poorly understood. Here, we investigated the regulatory mechanisms between Smad3 and the clock genes Dec1, Dec2, and Per1. In Smad3 knockout mice, the amplitude of locomotor activity was decreased, and Dec1 expression was decreased in the suprachiasmatic nucleus, liver, kidney, and tongue compared with control mice. Conversely, Dec2 and Per1 expression was increased compared with that of control mice. In Smad3 knockout mice, immunohistochemical staining revealed that Dec1 expression decreased, whereas Dec2 and Per1 expression increased in the endothelial cells of the kidney and liver. In NIH3T3 cells, Smad3 overexpression increased Dec1 expression, but decreased Dec2 and Per1 expression. In a wound-healing experiment that used Smad3 knockout mice, Dec1 expression decreased in the basal cells of squamous epithelium, promoting wound healing of the mucosa. Finally, the migration and proliferation of Smad3 knockdown squamous carcinoma cells was suppressed by Dec1 overexpression but was promoted by Dec2 overexpression. Dec1 overexpression decreased E-cadherin and proliferating cell nuclear antigen expression, whereas these expression levels were increased by Dec2 overexpression. These results suggest Smad3 is relevant to circadian rhythm and regulates cell migration and proliferation through Dec1, Dec2, and Per1 expression.

Functional Reorganization in the Primary Somatosensory Cortex of Rat Following Hind-Paw Amputation: A Study of Functional Imaging with 1.5 Tesla MRI.

To learn how rat primary somatosensory cortex (pSSC) responses to the loss of inputs from hind-paw, using fMRI of an inferior magnetic power (1.5 Tesla) with special designed high-powered rat coil. Ten adult male Sprague-Dawley rats were enrolled in this study. The rats were anesthetized with ketamine injection. Xylazine was intraperitoneally injected for analgesia and muscle relaxation with careful maintenance of spontaneous respiration. Either right or left hind-paws were amputated under aseptic conditions according to predefined random allocation of the rats. A 12-channel rat surface coil developed for proper image resolution in 1.5 Tesla MR was used. Functional magnetic resonance imaging was obtained before hind-paw amputation; 2, 15 and 30 days after the amputation. Activation signals were detected in 5 rats' contralateral pSSC before the hind-paw amputation with regression and cessation of the signal after the amputation. Signal re-appeared in the contralateral pSSC of only one rat (rat 9) 30 days after the amputation. This study showed that functional plasticity might occur in the pSSC following hind-paw amputation of rats. Further studies are necessary to understand the true nature of the plasticity observed in pSSC, with new and novel measurement techniques on cellular basis rather than gross anatomical one.

Comparative Effect of Intravenous Ketamine and Electroconvulsive Therapy in Major Depression: A Randomized Controlled Trial

Background:Achieving a rapid onset and durable methods of treatment for major depressive disorders is an issue pursuing in psychiatry. This study was designed to assess the therapeutic efficacy of intravenous (IV) ketamine injection in controlling depressive symptoms in comparison with electroconvulsive therapy (ECT) in major depressed disordered patients.Materials and Methods:Thirty-two patients over 18 years of age who were candidates for ECT were enrolled in the study. They were allocated into two groups using block design randomization. Sixteen patients received IV infusion of 0.5-mg/kg ketamine and 16 patients underwent a bitemporal ECT. To evaluate the changes in depression severity, researchers administered Hamilton Depression Rating Scale (HDRS) at baseline, before each treatment session, and four time points posttreatment (week 1 and months 1, 2, and 3). The Wechsler Memory Scale was used to evaluate the cognitive state of patients in week 1, month 1, and month 3 of the treatment.Results:The HDRS showed improvement in depressive symptoms in both the groups with no statistically significant difference. Cognitive state was more favorable (but not significant) in the ketamine group (P > 0.5).Conclusion:Treatment with IV ketamine in depressed people has the same antidepressant effects as ECT treatment without any memory deficiency.

To compare the efficacy of preemptive oral pregabalin versus oral pregabalin with intravenous ketamine as premedication on early postoperative pain

Background and Objectives: Using opioid alone for postoperative pain relief is usually inadequate, and higher doses can cause a multitude of complications. A drug, which has anxiolytic property without the adverse effects of traditional analgesics mentioned, may be an attractive choice for postoperative analgesia. This study was done to compare analgesic efficacy of different nonopioid drugs on early postoperative pain and thus opioid-sparing effect. Materials and Methods: It was a randomized controlled trial. Sixty patients scheduled to undergo elective abdominal surgery under general anesthesia were assessed in the study. Primary Objective: The primary objective of this study was to observe the effect of preemptive pregabalin and pregabalin with intravenous (IV) ketamine on Cumulative analgesic requirement postoperatively. Secondary Objective: The secondary objective of this study was to observe the effect of preemptive pregabalin and pregabalin with IV ketamine on (1) analgesia and (2) adverse effects. Patients were randomly divided into two groups each containing 30 patients. Group P received 150 mg of oral pregabalin, 2 h before induction of anesthesia. Group PK received 150 mg of oral pregabalin, 2 h before induction of anesthesia, and injection ketamine 0.15 mg/kg intravenously just before induction of anesthesia. Heart rate and mean blood pressure (MBP) were observed and recorded at different time intervals during surgery. Heart rate, MBP, time to first analgesic demand, visual analog scale (VAS) score, total postoperative analgesic requirement, sedation score, and side effects were recorded in postoperative period. Results: In Group P, the mean total analgesia requirement in postoperative period was 44.47 ± 5.06 mg, whereas in Group PK, it was 41.8 ± 2.34 mg (P = 0.006). VAS score and time to first analgesic demand were insignificantly higher in Group P. No statistically significant difference was found in side effect profile among the two groups. Conclusion: From our study, it could be concluded that a combination of oral pregabalin and IV ketamine when administered preoperatively can decrease opioid consumption while providing good pain control.