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1.
J Cardiothorac Vasc Anesth ; 37(1): 65-72, 2023 01.
Article in English | MEDLINE | ID: mdl-36307353

ABSTRACT

OBJECTIVE: The authors aimed to compare the anti-inflammatory and antioxidant effects of propofol and sevoflurane in children with cyanotic congenital heart disease (CCHD) undergoing cardiac surgery with cardiopulmonary bypass. DESIGN: Prospective, randomized, double-blind study. SETTING: Single center, university hospital. PARTICIPANTS: Children ages 1-10 years with CCHD undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Children were randomized to receive general anesthesia with either sevoflurane (group S) or propofol (group P). Systemic inflammatory response syndrome (SIRS) occurrence was assessed at the end of the surgery and at the sixth, 12th, and 24th postoperative hours. Blood samples were obtained at 4 times: after anesthesia induction (T0), after release of the aortic cross-clamp (T1), at the end of the surgery (T2), and at the postoperative 24th hour (T3). The serum levels of interleukin 6 and tumor necrosis factor alpha, and the total antioxidant status (TAS) and total oxidant status, were analyzed. RESULTS: SIRS was more common in group S than in group P at all times (p = 0.020, p = 0.036, p = 0.004, p = 0.008). There were no significant differences between the groups in the mean tumor necrosis factor alpha and interleukin 6 levels at any time. The TAS level at T2 was higher in group P than group S (p = 0.036). The serum TAS level increased at T2 compared with T0 in group P, but it decreased in group S (p = 0.041). CONCLUSION: The results showed that propofol provided a greater antioxidant effect and reduced SIRS postoperatively more than sevoflurane in children with CCHD undergoing cardiac surgery.


Subject(s)
Anti-Inflammatory Agents , Antioxidants , Heart Defects, Congenital , Propofol , Sevoflurane , Child , Child, Preschool , Humans , Infant , Anesthetics, Inhalation/therapeutic use , Anesthetics, Intravenous/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use , Cyanosis , Heart Defects, Congenital/surgery , Interleukin-6 , Propofol/therapeutic use , Prospective Studies , Sevoflurane/therapeutic use , Systemic Inflammatory Response Syndrome , Tumor Necrosis Factor-alpha
2.
Gene Ther ; 29(7-8): 441-448, 2022 Aug.
Article in English | MEDLINE | ID: mdl-34599290

ABSTRACT

Acrodysostosis is a rare skeletal dysplasia caused by loss-of-function mutations in the regulatory subunit of protein kinase A (PRKAR1A). In a knock-in mouse model (PRKAR1Awt/mut) expressing one copy of the recurrent R368X mutation, we tested the effects of a rAAV9-CAG-human PRKR1A (hPRKAR1A) vector intravenously administered at 4 weeks of age. Caudal vertebrae and tibial diaphyses contained 0.52 ± 0.7 and 0.13 ± 0.3 vector genome per cell (VGC), respectively, at 10 weeks of age and 0.22 ± 0.04 and 0.020 ± 0.04 at 16 weeks while renal cortex contained 0.57 ± 0.14 and 0.26 ± 0.05 VGC. Vector-mediated hPRKAR1A expression was found in growth plate chondrocytes, osteoclasts, osteoblasts, and kidney tubular cells. Chondrocyte architecture was restored in the growth plates. Body length, tail length, and body weight were improved in vector treated PRKAR1Awt/mut mice, not the bone length of their limbs. These results provide one of the few proofs for gene therapy efficacy in a mouse model of chondrodysplasia. In addition, the increased urinary cAMP of PRKAR1Awt/mut mice was corrected almost to normal. In conclusion, gene therapy with hPRKAR1A improved skeletal growth and kidney dysfunction, the hallmarks of acrodysostosis in R368X mutated mice and humans.

3.
J Cardiothorac Vasc Anesth ; 33(2): 442-449, 2019 02.
Article in English | MEDLINE | ID: mdl-30049524

ABSTRACT

OBJECTIVE: To determine the blood sevoflurane and desflurane concentrations during one-lung ventilation (OLV). DESIGN: Randomized, single-blind study. SETTING: Single university hospital. PARTICIPANTS: The study comprised 24 patients, 35 to 70 years old who were scheduled for either a major abdominal surgery or thoracotomy. INTERVENTIONS: The patients were divided into the following 4 groups: sevoflurane two-lung ventilation (TLV), sevoflurane OLV, desflurane TLV, and desflurane OLV. Vaporizers were set at 1.5% sevoflurane or 6% desflurane. MEASUREMENTS AND MAIN RESULTS: In the TLV groups, blood samples were taken in 10-minute intervals starting 40 minutes after the start of TLV (T1-T9) for blood gas analysis and gas chromatography. In the OLV groups, the first sample was collected at 40 minutes of TLV (T1), and other samples were collected in 10-minute intervals from the start of OLV (T2-T9). Saturation of peripheral oxygen (SpO2), hemodynamic variables, and inspired and end-tidal volatiles were recorded. The fraction uptake of the volatile agents (F) was calculated for each patient at the same time points. The mean arterial sevoflurane concentration in the sevoflurane OLV group at T1 decreased from 40.7 ± 4.4 to 30.2 ± 2.5 µg/mL at T3 (p = 0.014, 26% decrease). In the OLV desflurane group, the mean arterial desflurane concentration at T1 declined from 224.6 ± 44.8 to 159.8 ± 32 µg/mL at T3 (p=0.018, 29% decrease). However, the reduction of sevoflurane concentration compared with that of desflurane at T3 was not statistically significant (p = 0.31). In addition, the fraction uptake of the volatile agents values significantly increased at the start of OLV (p = 0.001). CONCLUSION: An OLV procedure causes a decrease in the both arterial and venous blood concentrations of sevoflurane and desflurane. This reduction is believed to be due to ventilation-perfusion mismatch.


Subject(s)
Anesthesia, General/methods , Desflurane/pharmacokinetics , Hypoxia/blood , Monitoring, Intraoperative/methods , One-Lung Ventilation/methods , Sevoflurane/pharmacokinetics , Adult , Aged , Anesthetics, Inhalation/pharmacokinetics , Biomarkers/blood , Blood Gas Analysis , Chromatography, Gas , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Single-Blind Method , Thoracic Surgical Procedures
4.
BMC Anesthesiol ; 18(1): 24, 2018 02 17.
Article in English | MEDLINE | ID: mdl-29454333

ABSTRACT

BACKGROUND: Percutaneous nephrolithotomy (PCNL) is a minimally invasive surgical procedure for renal calculi, and nephrostomy tubes lead to postoperative pain after PCNL. Regional techniques (e.g., epidural analgesia and peripheral blocks) and opioids are applied for postoperative pain treatment. The aim of this study was to compare effectiveness of ultrasound-guided paravertebral block (PVB) and tramadol on postoperative pain in patients who underwent PCNL. METHOD: Fifty-three patients were included in this prospective randomized study. The patients were allocated into two groups: the PVB group (group P, n = 26) and the tramadol group (group T, n = 27). All patients were administered standard general anaesthesia. Ultrasound-guided PVB was performed at the T11- L1 levels using 0.5% bupivacaine for a total dose of 15 mL in group P. Patients in group T were intravenously administered a loading dose of 1 mg/kg tramadol. Patients in both groups were given patient-controlled analgesia. Haemodynamic parameters, visual analogue scale (VAS) scores, side effects, and complications, tramadol consumption and additional analgesic requirements of the patients were recorded after surgery. RESULTS: Haemodynamic parameters were statistically similar between the groups. The VAS in group P were statistically lower than in group T. In the 24-h period after surgery, total PCA tramadol consumption was statistically lower in group P than in group T. The use of supplemental analgesic in group T was higher than in group P. CONCLUSIONS: Ultrasound-guided PVB was found to be an effective analgesia compared to tramadol, and no additional complications were encountered. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02412930 , date of registration: March 27, 2015, retrospectively registered.


Subject(s)
Analgesics, Opioid/therapeutic use , Nephrolithotomy, Percutaneous , Nerve Block/methods , Pain, Postoperative/drug therapy , Tramadol/therapeutic use , Ultrasonography, Interventional/methods , Adult , Analgesics, Opioid/administration & dosage , Female , Humans , Male , Prospective Studies , Tramadol/administration & dosage , Treatment Outcome
5.
Turk J Med Sci ; 47(5): 1403-1409, 2017 11 13.
Article in English | MEDLINE | ID: mdl-29151310

ABSTRACT

Background/aim: Myocardial protection is an important factor of open heart surgery and biological biomarkers (lactate, CKMB, cardiac troponin I, and pyruvate) are used to assess myocardial damage. This study compares the effects of dexmedetomidine and remifentanil on myocardial protection during coronary artery bypass grafting (CABG) surgery. Materials and methods: Patients scheduled for elective CABG surgery (n = 60) were included in this study. Anesthesia induction was introduced with propofol, fentanyl, and vecuronium bromide. Anesthesia was maintained with remifentanil infusion and sevoflurane in the remifentanil group (Group R) and with dexmedetomidine infusion and sevoflurane in the dexmedetomidine group (Group D). Blood samples for biochemical markers were taken from the coronary sinus catheter before cardiopulmonary bypass (T1), 20 min after aortic cross-clamping (T2), 20 min after removal of the aortic cross-clamping (T3), and 10 min after separation from cardiopulmonary bypass (T4).Results: Demographic data were similar between the groups. Lactate level at the T2 period and CKMB levels during the study period were lower in Group D than in Group R. In both groups, all values except pyruvate significantly increased over time. Conclusion: The dexmedetomidine-sevoflurane combination may improve the cardioprotective effect in comparison with remifentanil-sevoflurane in CABG surgery.

6.
N Engl J Med ; 364(23): 2218-26, 2011 Jun 09.
Article in English | MEDLINE | ID: mdl-21651393

ABSTRACT

The skeletal dysplasia characteristic of acrodysostosis resembles the Albright's hereditary osteodystrophy seen in patients with pseudohypoparathyroidism type 1a, but defects in the α-stimulatory subunit of the G-protein (GNAS), the cause of pseudohypoparathyroidism type 1a, are not present in patients with acrodysostosis. We report a germ-line mutation in the gene encoding PRKAR1A, the cyclic AMP (cAMP)-dependent regulatory subunit of protein kinase A, in three unrelated patients with acrodysostosis and resistance to multiple hormones. The mutated subunit impairs the protein kinase A response to stimulation by cAMP; this explains our patients' hormone resistance and the similarities of their skeletal abnormalities with those observed in patients with pseudohypoparathyroidism type 1a.


Subject(s)
Cyclic AMP-Dependent Protein Kinase RIalpha Subunit/genetics , Cyclic AMP-Dependent Protein Kinases/metabolism , Germ-Line Mutation , Hormones/metabolism , Adolescent , Child , Cyclic AMP-Dependent Protein Kinase RIalpha Subunit/metabolism , Drug Resistance , Dysostoses/genetics , Dysostoses/metabolism , Female , Humans , Intellectual Disability/genetics , Intellectual Disability/metabolism , Male , Osteochondrodysplasias/genetics , Osteochondrodysplasias/metabolism , Parathyroid Hormone/metabolism , Pedigree , Transcription, Genetic , Young Adult
7.
J Cell Biol ; 177(3): 451-64, 2007 May 07.
Article in English | MEDLINE | ID: mdl-17470636

ABSTRACT

Recent evidence suggests that low oxygen tension (hypoxia) may control fetal development and differentiation. A crucial mediator of the adaptive response of cells to hypoxia is the transcription factor Hif-1alpha. In this study, we provide evidence that mesenchymal condensations that give origin to endochondral bones are hypoxic during fetal development, and we demonstrate that Hif-1alpha is expressed and transcriptionally active in limb bud mesenchyme and in mesenchymal condensations. To investigate the role of Hif-1alpha in mesenchymal condensations and in early chondrogenesis, we conditionally inactivated Hif-1alpha in limb bud mesenchyme using a Prx1 promoter-driven Cre transgenic mouse. Conditional knockout of Hif-1alpha in limb bud mesenchyme does not impair mesenchyme condensation, but alters the formation of the cartilaginous primordia. Late hypertrophic differentiation is also affected as a result of the delay in early chondrogenesis. In addition, mutant mice show a striking impairment of joint development. Our study demonstrates a crucial, and previously unrecognized, role of Hif-1alpha in early chondrogenesis and joint formation.


Subject(s)
Chondrogenesis/physiology , Hindlimb/embryology , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Joints/embryology , Mesoderm/metabolism , Animals , Cell Hypoxia/physiology , Female , Hindlimb/cytology , Hypoxia-Inducible Factor 1, alpha Subunit/deficiency , Joints/cytology , Mesoderm/cytology , Mice , Mice, Knockout , Pregnancy
8.
Middle East J Anaesthesiol ; 21(4): 613-8, 2012 Feb.
Article in English | MEDLINE | ID: mdl-23327035

ABSTRACT

The primary aim of this study was to test whether dexmedetomidine administration based on the bispectral index (BIS) monitoring caused a reduction in consumption of sevoflurane. Following Institutional Ethic Committee approval and written informed consent from all parents, fifty-four children undergoing sevoflurane anaesthesia randomly allocated to receive either dexmedetomidine (Group D) or saline (Group S). The anaesthesia was induced with 8% sevoflurane in nitrous oxide/oxygen in all children. Following anaesthesia induction, Group D (n=27) children received a loading dose of dexmedetomidine 1 microgkg(-1) IV over ten minutes, followed by a continuous infusion at a rate of 0.5 microgkg(-1) hr(-1) throughout the surgery. Group S (n = 27) children received same volume of saline infusion due to obtained blindness. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), body temperature and peripheral oxygen saturation (SpO2), end-tidal concentrations of oxygen, carbon dioxide (ETCO2), and sevoflurane (ETsevo) were monitorized. Bispectral index numbers and ETsevo concentrations were recorded at 2 min before incision, 2 min after incision, at the end of surgery and before the termination of anaesthesia, and finally immediately after wake-up from anaesthesia (Final BIS number). BIS number was found significantly lower in group D at before incision, after incision and at the end of surgery than in group S (p = 0.000, 0.001, 0.007). End tidal sevoflurane concentrations were significantly higher in group S at before incision, after incision and at the end of surgery than in group D (p < 0.000 to p < 0.001). Final BIS number and sevoflurane concentrations were similar and there were no significant difference between the groups. It was concluded that intravenous (IV) dexmedetomidine infusion at a rate of 0.5 microgkg(-1) hr(-1) during sevoflurane anaesthesia significantly reduces end-tidal sevoflurane concentration and BIS number in children undergoing minor surgical interventions.


Subject(s)
Anesthetics, Inhalation/administration & dosage , Dexmedetomidine/pharmacology , Hypnotics and Sedatives/pharmacology , Methyl Ethers/administration & dosage , Blood Pressure , Body Temperature , Child , Child, Preschool , Consciousness Monitors , Dexmedetomidine/administration & dosage , Double-Blind Method , Female , Heart Rate , Humans , Hypnotics and Sedatives/administration & dosage , Infusions, Intravenous , Male , Monitoring, Intraoperative/methods , Nitrous Oxide/administration & dosage , Oxygen/administration & dosage , Oxygen/metabolism , Prospective Studies , Sevoflurane
9.
Hum Gene Ther ; 33(17-18): 936-949, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35166123

ABSTRACT

Adrenomyeloneuropathy (AMN) is a late-onset axonopathy of spinal cord tracts caused by mutations of the ABCD1 gene that encodes adrenoleukodystrophy protein (ALDP), a peroxisomal transporter of very long-chain fatty acids (VLCFA). Disturbed metabolic interaction between oligodendrocytes (OL) and axons is suspected to play a major role in AMN axonopathy. To develop a vector targeting OL, the human ABCD1 gene driven by a short 0.3 kb part of the human myelin-associated glycoprotein (MAG) promoter was packaged into an adeno-associated viral serotype 9 (rAAV9). An intravenous injection of this vector on postnatal day 10 in Abcd1-/- mice, a model of AMN, allowed a near normal motor performance to persist for 24 months, while age-matched untreated mice developed major defects of balance and motricity. Three weeks postvector, 50-54% of spinal cord white matter OL was expressing human ALDP (hALDP) at the cervical level, and only 6-7% after 24 months. In addition, 29-32% of cervical spinal cord astrocytes at 3 weeks and 16-19% at 24 months also expressed ALDP. C26:0-lysoPC, a sensitive VLCFA marker of AMN, was lower by 41% and 50%, respectively, in the spinal cord and brain of vector-treated compared with untreated mice. In a nonhuman primate, the intrathecal injection of the rAAV9-MAG vector induced abundant ALDP expression at 3 weeks in spinal cord OL (43%, 29%, and 26% at cervical, thoracic, and lumbar levels) and cerebellum OL (35%). In addition, 33-41% of spinal cord astrocytes expressed hALDP, and 27% of cerebellar astrocytes. To our knowledge, OL targeting had not been obtained before in primates with other vectors or promoters. The current results thus provide a robust proof-of-concept not only for the gene therapy of AMN but also for other central nervous system diseases, where the targeting of OL with the rAAV9-MAG vector may be of interest.


Subject(s)
Adrenoleukodystrophy , ATP Binding Cassette Transporter, Subfamily D, Member 1/genetics , Adrenoleukodystrophy/genetics , Adrenoleukodystrophy/therapy , Animals , Disease Models, Animal , Fatty Acids/metabolism , Genetic Therapy , Humans , Mice , Myelin-Associated Glycoprotein/genetics , Myelin-Associated Glycoprotein/metabolism , Oligodendroglia/metabolism
10.
J Anesth ; 25(2): 184-8, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21327805

ABSTRACT

PURPOSE: Several studies have reported that sevoflurane was associated with a relatively high incidence of emergence agitation in children even in the absence of any surgical intervention. The aim of this study was to compare early agitation characteristics of oral melatonin, dexmedetomidine, and midazolam premedication in children who were given sevoflurane anesthesia for esophageal dilatation. METHODS: Following Internal Review Board approval and parental informed consent, 100 ASA physical status I-II children (3-9 years old) who were scheduled to undergo general anesthesia for esophageal dilatation procedures were enrolled. The patients were randomly assigned to four groups (n = 25 in each). The premedications in the groups were saline (group P), dexmedetomidine 2.5 µg/kg (group D), 0.5 mg/kg midazolam (group MD), and melatonin 0.1 mg/kg (group ML), given orally. All premedication drugs were given with paracetamol 2-2.5 mg/kg to be easily drinkable 40-45 min before anesthesia induction. Anesthesia was maintained with sevoflurane 2-4%, N(2)O 50% in oxygen. No supplemental analgesic agent was given, and an emergence agitation scale (EAS) was measured on admission to the PACU, then every 5 min, and recorded during the postoperative period: 1, awake and calm, cooperative; 2, crying, requires consoling; 3, irritable/restless, screaming, inconsolable; 4, combative, disoriented, thrashing. Children with an agitation score of 3 or 4 were classified as agitated. RESULTS: There were no significant differences among the four groups demographically. The emergence agitation scale was higher in the placebo group than in the others at 5, 10, and 15 min postoperatively (P < 0.001). EA was similar among group D, group MD, and group ML. CONCLUSION: We found that oral melatonin, dexmedetomidine, and midazolam reduced the incidence of emergence agitation in children after sevoflurane anesthesia.


Subject(s)
Dexmedetomidine/therapeutic use , Melatonin/therapeutic use , Midazolam/therapeutic use , Postoperative Complications/prevention & control , Preanesthetic Medication , Psychomotor Agitation/prevention & control , Administration, Oral , Child , Child, Preschool , Dexmedetomidine/administration & dosage , Female , Humans , Male , Melatonin/administration & dosage , Methyl Ethers/adverse effects , Midazolam/administration & dosage , Sevoflurane
11.
J Anesth ; 24(5): 700-4, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20665055

ABSTRACT

PURPOSE: In this study, we aimed to compare the effects of ropivacaine alone and ropivacaine plus tramadol administered epidurally for postoperative analgesia in children. METHODS: Following Ethics Committee approval and informed parent consent, 44 children aged between 2 and 12 years, with ASA physical status I or II, who were undergoing major abdominal surgery were included in the study. Following tracheal intubation, patients were placed into lateral decubitus position and an epidural catheter (22-24 G) was inserted by using a Tuohy needle. Patients were randomly divided into two groups to receive either ropivacaine alone (0.2%), 0.7 ml/kg, in group I, or ropivacaine (0.2%) plus tramadol (2 mg/kg), with total volume 0.7 ml/kg, in group II, epidurally in both groups. Hemodynamic variables, pain and sedation scores, duration of analgesia, and side effects were recorded postoperatively. RESULTS: The duration of analgesia was significantly longer in group RT than in group R (298.6 ± 28 and 867.9 ± 106.8 min in group I and II, respectively) (P < 0.05). CHEOPS scores were significantly lower in group RT at 30 min, 45 min, and 3 h postoperatively than in group R (P < 0.05). However, sedation scores were similar between the two groups. Twenty-two patients (100%) in group R and 13 patients (59%) in group RT needed supplemental analgesia postoperatively. There were no significant differences in side effects between the groups. CONCLUSION: In children undergoing major abdominal surgery, epidural tramadol, added to epidural ropivacaine, provided lower pain scores, longer duration of analgesia, and lower postoperative analgesic requirement.


Subject(s)
Abdomen/surgery , Amides/therapeutic use , Analgesics, Opioid/therapeutic use , Anesthesia, Epidural , Anesthetics, Local/therapeutic use , Pain, Postoperative/drug therapy , Tramadol/therapeutic use , Amides/administration & dosage , Analgesics, Opioid/administration & dosage , Anesthesia, General , Anesthetics, Local/administration & dosage , Blood Gas Analysis , Child , Child, Preschool , Female , Hemodynamics/physiology , Humans , Male , Monitoring, Intraoperative , Pain Measurement/drug effects , Ropivacaine , Sample Size , Tramadol/administration & dosage , Urologic Surgical Procedures
12.
Braz J Anesthesiol ; 68(6): 597-604, 2018.
Article in Portuguese | MEDLINE | ID: mdl-30205906

ABSTRACT

BACKGROUND AND OBJECTIVES: Pediatric patients frequently require deep sedation or general anesthesia for colonoscopy. This study was designed to compare the sedative efficacy of remifentanil-ketamine combination with propofol-ketamine combination in children undergoing colonoscopy. METHODS: Seventy patients, between 2 and 16 years of age, scheduled for diagnostic colonoscopy were randomly allocated into two groups. Remifentanil-ketamine group received intravenous ketamine 2mg.kg-1 and remifentanil 0.25µg.kg-1 combination, followed by 0.1µg.kg-1.min-1 remifentanil infusion. Propofol-ketamine group received intravenous propofol 1 and 2mg.kg-1 ketamine combination, followed by 1mg.kg-1.h-1 propofol infusion. In the case of children discomfort (cry, movement, and cough), remifentanil 0.1µg.kg-1 in the remifentanil-ketamine group or propofol 0.5mg.kg-1 in the propofol-ketamine group were administered to improve children discomfort. Despite the therapy given above, if children still experience discomfort, 1mg.kg-1 of ketamine was administered as a rescue drug, regardless of the group. Ramsay sedation score, hemodynamic variables, drug requirements, gastroenterologists' satisfaction, colonoscopy duration, recovery time, and side effects were recorded throughout the procedure and the recovery period. RESULTS: The percentage of patients with a Ramsay sedation score of 4 or higher during the procedure was 73.5 and 37.1% in remifentanil-ketamine and propofol-ketamine groups, respectively (p=0.02). Systolic and diastolic blood pressure variables were significantly higher only after induction in the remifentanil-ketamine group than in the propofol-ketamine group (p=0.015). CONCLUSION: Coadministration of ketamine with either remifentanil or propofol effectively and safely provides sedation and analgesia in children undergoing colonoscopy. Sedation scores were significantly better in remifentanil-ketamine group than in propofol-ketamine group.


Subject(s)
Analgesics, Opioid/administration & dosage , Anesthetics, Dissociative/administration & dosage , Colonoscopy , Deep Sedation/methods , Hypnotics and Sedatives/administration & dosage , Ketamine/administration & dosage , Propofol/administration & dosage , Remifentanil/administration & dosage , Child , Double-Blind Method , Drug Combinations , Female , Humans , Male , Prospective Studies
13.
Eur J Pharmacol ; 572(2-3): 138-41, 2007 Oct 31.
Article in English | MEDLINE | ID: mdl-17628526

ABSTRACT

Previous studies has report the modulation of K+ channels play key roles in the induction of peripheral antinociception induced by many types of drugs. However, the possible participation of 4-aminopyridine-sensitive K+ channels to local antinociception induced by tramadol, a mu opioid receptor agonist, and lidocaine, a local anaesthetic, has been less studied. In this study, we therefore investigated this by using thermal plantar test. Tramadol or lidocaine administered intraplantarly into the hind paw elicited an antinociceptive effect. 4-aminopyridine caused an increase in the antinociception produced by lidocaine. However, tramadol induced antinociception remained unaffected by intraplantar administration of 4-aminopyridine. These results suggest that 4-aminopyridine-sensitive K+ channels may play an important role in the thermal peripheral antinociception produced by lidocaine, but not tramadol.


Subject(s)
4-Aminopyridine/pharmacology , Lidocaine/pharmacology , Pain/metabolism , Potassium Channel Blockers/pharmacology , Potassium Channels/physiology , Tramadol/pharmacology , Anesthetics, Local/pharmacology , Animals , Female , Rats , Rats, Wistar , Receptors, Opioid, mu/agonists
14.
Eur J Pharmacol ; 558(1-3): 68-72, 2007 Mar 08.
Article in English | MEDLINE | ID: mdl-17196585

ABSTRACT

Several studies have suggested that systemic tramadol, an opioid, can represent a valuable treatment in severe pain conditions because of their effects on central pain pathways. However, there are not enough studies supporting that tramadol is efficacious when administered locally. Therefore, we studied the potential local analgesic effects of tramadol in peripheral nociception. In addition, we tested the antinociceptive effects of tramadol-CaCl(2) or naloxone combinations after subcutaneous intraplantar injection in a validated rat model of acute thermal nociception. Local analgesic effects of tramadol were compared with those of lidocaine. The effects of tramadol on thermal paw withdrawal latencies were monitored using the plantar test. The antinociceptive potency of tramadol is higher and long-lasting than that of lidocaine. Naloxone was unable to inhibit the increased antinociceptive response produced by tramadol. Ca(2+) modified the effect of tramadol. When Ca(2+) dose was increased in the solution, thermal antinociceptive potency of tramadol, but not lidocaine was prolonged. Thermal nociceptive responses were not affected in the non-injected paws, indicating a lack of systemic effects with doses of tramadol and lidocaine that elicited local analgesia. These results suggest that intraplantar tramadol administration can produce local analgesic effect with a different action mechanism than that of lidocaine. In addition, extracellular Ca(2+) may play an important role in the local analgesic action of tramadol.


Subject(s)
Analgesics, Opioid/administration & dosage , Tramadol/administration & dosage , Animals , Calcium Chloride/pharmacology , Female , Injections , Lidocaine/pharmacology , Rats , Rats, Wistar , Reaction Time/drug effects , Tramadol/pharmacology
15.
Agri ; 19(1): 36-41, 2007 Jan.
Article in Turkish | MEDLINE | ID: mdl-17457705

ABSTRACT

In this study, we aimed to assess the effect of administration of ondansetron on morphine and tramadol consumptions. After approval by the ethics committee, 120 patients with ASA status I or II, who will undergo elective lower extremity surgery, were included in the study. Patients were randomly divided into 4 groups following the anesthesia induction. Group I received tramadol as PCA with an infusion of 0.3 mg/kg following a loading dose of 1.5 mg/kg administered 1 hour before the end of the surgery. Group II received ondansetron 0.1 mg/kg following induction of anesthesia, additionally. Group III received morphine as PCA with an infusion following a loading dose of 0.15 mg/kg administered 30 minutes before the end of surgery. Group IV received ondansetron 0.1 mg/kg following induction of anesthesia, additionally. Pain scores(VAS), nausea, vomitting and sedation scores, analgesic consumptions and adverse effects were recorded at 5th, 15th, 30th, 45th minutes and 4th, 8th, 12th and 24th hours postoperatively. Postoperative VAS, nausea, vomitting and sedation scores were similar among the groups. The analgesic consumption was found significantly higher at 4th, 8th, 12th and 24th hours in group II. No statistically significant difference was found in analgesic consumption between group III and IV at all times. We concluded that, ondansetron, when administered as nausea prophylaxis in patients receiving tramadol and morphine as PCA, did not effect morphine consumption whereas did increased tramadol consumption.


Subject(s)
Analgesics, Opioid/therapeutic use , Anti-Anxiety Agents/therapeutic use , Bone Diseases/surgery , Ondansetron/therapeutic use , Pain, Postoperative/prevention & control , Adult , Analgesia, Patient-Controlled , Analgesics, Opioid/administration & dosage , Anti-Anxiety Agents/administration & dosage , Drug Administration Schedule , Drug Therapy, Combination , Female , Humans , Leg/surgery , Male , Middle Aged , Morphine/administration & dosage , Morphine/therapeutic use , Ondansetron/administration & dosage , Pain Measurement , Tramadol/administration & dosage , Tramadol/therapeutic use , Treatment Outcome
16.
Agri ; 29(4): 162-166, 2017 Oct.
Article in Turkish | MEDLINE | ID: mdl-29171646

ABSTRACT

OBJECTIVES: In this study, we aimed to determine the effect of remifentanil administration prior to slow and fast rocuronium infusion on hemodynamic changes and rocuronium injection pain in pediatric patients. METHODS: In total, 120 5-15-year-old ASA score I/II pediatric patients were included in the study. Group A: slow rocuronium injection-saline; group B: slow rocuronium injection (0.6 mg/kg IV)-remifentanyl; group C: fast rocuronium injection-saline; and group D: fast rocuronium injection-remifentanyl. Withdrawal movement after rocuronium injection was recorded based on a 3-point response to withdrawal score. Hemodynamic parameters were recorded. RESULTS: One minute after rocuronium injection, HR values were found to be lower in remifentanil groups (p: 0.0001; 101.4±22.1, p: 0.003; 99.8±18.3 in group B and D, respectively) compared with those in placebo groups (p: 0.025; 107.4±21.7, p: 0.012; 114.0±16.4 in group A and C, respectively). With respect to the response to withdrawal scores, unresponsiveness rates were the highest in group B (66.7%) and group D (70%). The number of non-responder patients was 9 in saline-administered groups (group A and C), whereas it was 20 and 21 in remifentanil-administered groups (group B and D, respectively). Generalized responses were observed predominantly in groups A (20%) and C (20%). Generalized responses were highest in groups A (20%, n=6) and C (20%, n=6). CONCLUSION: There was no impact of infusion speed on rocuronium injection pain in pediatric cases, whereas it is concluded that remifentanil administration prior to rocuronium injection considerably reduced rocuronium injection pain regardless of injection speed and without serious hemodynamic changes.


Subject(s)
Analgesics, Opioid/administration & dosage , Androstanols/administration & dosage , Anesthesia, General , Neuromuscular Nondepolarizing Agents/administration & dosage , Piperidines/administration & dosage , Adolescent , Child , Child, Preschool , Drug Administration Schedule , Female , Humans , Injections, Intravenous/adverse effects , Male , Pain Measurement , Remifentanil , Rocuronium , Treatment Outcome
17.
Eur J Pharmacol ; 543(1-3): 54-62, 2006 Aug 14.
Article in English | MEDLINE | ID: mdl-16822495

ABSTRACT

The aim of the present study was to investigate the action of lidocaine and tramadol on the abnormal impulse characteristics of injured peripheral nerves. The ultrastructure of nerves was studied with electron microscopy and the action of lidocaine and tramadol on intact and injured rat sciatic nerves was examined by using the sucrose gap recording technique. Tramadol and lidocaine caused concentration- and frequency-dependent decreases in the amplitude of the compound action potential. Injured nerves were more sensitive to lidocaine than to tramadol. Lidocaine suppressed the delayed depolarization and decreased the hyperpolarizing afterpotentials to a greater extent than did tramadol. A low concentration of lidocaine may restore the abnormal impulse characteristics of injured nerves without changing the normal impulse pattern. The efficacy of lidocaine and inefficacy of tramadol on abnormal impulse characteristics may contribute, at least in part, to our understanding of the mechanisms of action of these drugs in neuropathic pain therapy.


Subject(s)
Analgesics, Opioid/pharmacology , Anesthetics, Local/pharmacology , Lidocaine/pharmacology , Sciatic Nerve/drug effects , Tramadol/pharmacology , 4-Aminopyridine/pharmacology , Action Potentials/drug effects , Analgesics, Opioid/therapeutic use , Anesthetics, Local/therapeutic use , Animals , Dose-Response Relationship, Drug , Electric Stimulation , Electrophysiology , Female , Lidocaine/therapeutic use , Neural Conduction/drug effects , Neuralgia/drug therapy , Neuralgia/metabolism , Potassium Channel Blockers/pharmacology , Rats , Rats, Wistar , Sciatic Nerve/metabolism , Sciatic Nerve/physiopathology , Sciatic Nerve/surgery , Sodium Channels/drug effects , Sodium Channels/metabolism , Time Factors , Tramadol/therapeutic use
18.
Minerva Anestesiol ; 82(5): 534-42, 2016 05.
Article in English | MEDLINE | ID: mdl-26474268

ABSTRACT

BACKGROUND: Anesthesia and surgery can lead to major distress for children. Sedative premedication and preoperative preparation techniques are available to reduce preoperative anxiety in children. We aimed to assess the effect of informational video based on role-play modelling on preoperative anxiety and postoperative behavior changes in children undergoing surgery. METHODS: Forty-two children aged 5-12 years, with American Society of Anesthesiologist physical status I-II, scheduled for elective outpatient surgery, were enrolled in this study. Patients were randomly allocated to one group with or without information video presentation. In group V, patients watched the information video (N.=21). Other children were verbally informed in a standard care (group C, N.=21). We recorded patient's demographics (age, birth order, surgery time, surgery type, history of previous surgery, parent's age, parental working status, parental education level), the preoperative anxiety level using Modified Yale Preoperative Anxiety Scale (MYPAS) and at 1 week after discharge, new developing postoperative maladaptive behaviors (POMB) using the Post Hospitalization Behavioral Questionnaire by telephone interview. RESULTS: Patient's demographics were similar in both groups. Total MYPAS scores were found to be lower in group V as compared to group C P=0.0001). Difficulty getting to sleep, nocturnal enuresis, fear of dark, to object to go to bed at night and decreased appetite of new developing POMB were found to be lower in group V than group C. We also found a correlation between anxiety scores and POMB. CONCLUSIONS: The presentation of an informational video based on model making reduces preoperative anxiety at the time of placement of the facemask and postoperative negative behavioral changes in children.


Subject(s)
Anxiety/prevention & control , Audiovisual Aids , Patient Education as Topic/methods , Postoperative Complications/prevention & control , Preoperative Care/methods , Child , Child, Preschool , Elective Surgical Procedures/psychology , Female , Humans , Hypnotics and Sedatives , Male , Parents , Patient Admission , Postoperative Period , Prospective Studies , Video Recording
19.
Neurol Res ; 27(1): 53-6, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15829159

ABSTRACT

OBJECTIVE: Congenital intracranial tumors are very rare and only account for 0.5-1.5% of all childhood brain tumors. The most common type of these tumors present at birth is teratomas, which represent 0.5% of all intracranial tumors. Most teratomas are midline tumors located predominantly in the sellar and pineal regions. In this study, we report a neonatal intracranial immature teratoma at the lateral ventricle because of its rare location. CASE REPORT: A 3-day-old female neonate presented with a history of irritability, vomiting, and recurrent generalized clonic seizures since birth. A head computed tomographic scan and magnetic resonance imaging disclosed a large tumor filling the right lateral ventricle and extending into the ipsilateral posterior fossa. With right parieto-occipital craniotomy, large grayish-white lobulated vascular mass was encountered and total removal of tumor was performed. Histological examination revealed the diagnosis of immature teratoma. CONCLUSION: The prognosis of congenital intracranial immature teratoma is usually poor because the lesions are extensive when they are identified. Prenatal ultrasonography is necessary for the prenatal diagnosis. Fetal magnetic resonance imaging should be made for the evaluation of intracranial tumor. If the tumor is detected before the 24 week of gestation, termination of the pregnancy should be considered.


Subject(s)
Cerebral Ventricle Neoplasms/congenital , Lateral Ventricles/pathology , Teratoma/congenital , Cerebral Ventricle Neoplasms/pathology , Child, Preschool , Female , Humans , Magnetic Resonance Imaging/methods , Review Literature as Topic , Teratoma/pathology , Tomography, X-Ray Computed/methods
20.
Mol Endocrinol ; 16(8): 1912-9, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12145344

ABSTRACT

XLalpha(s), the large variant of the stimulatory G protein alpha subunit (Gsalpha), is derived from GNAS1 through the use of an alternative first exon and promoter. Gs(alpha) and XLalpha(s) have distinct amino-terminal domains, but are identical over the carboxyl-terminal portion encoded by exons 2-13. XLalpha(s) can mimic some functions of Gs(alpha), including betagamma interaction and adenylyl cyclase stimulation. However, previous attempts to demonstrate coupling of XLalpha(s) to typically Gs-coupled receptors have not been successful. We now report the generation of murine cell lines that carry homozygous disruption of Gnas exon 2, and are therefore null for endogenous XLalpha(s) and Gs(alpha) (Gnas(E2-/E2-)). Gnas(E2-/E2-) cells transfected with plasmids encoding XLalpha(s) and different heptahelical receptors, including the beta2-adrenergic receptor and receptors for PTH, TSH, and CRF, showed agonist-mediated cAMP accumulation that was indistinguishable from that observed with cells transiently coexpressing Gs(alpha) and these receptors. Our findings thus indicate that XLalpha(s) is capable of functionally coupling to receptors that normally act via Gs(alpha).


Subject(s)
Adenylyl Cyclases/metabolism , GTP-Binding Protein alpha Subunits, Gs/metabolism , Heterotrimeric GTP-Binding Proteins/metabolism , Nerve Tissue Proteins , Alternative Splicing , Animals , Cell Line , Chromogranins , Enzyme Activation , Exons , GTP-Binding Protein alpha Subunits, Gs/chemistry , GTP-Binding Protein alpha Subunits, Gs/deficiency , GTP-Binding Protein alpha Subunits, Gs/genetics , Genetic Variation , Heterotrimeric GTP-Binding Proteins/chemistry , Heterotrimeric GTP-Binding Proteins/deficiency , Heterotrimeric GTP-Binding Proteins/genetics , Mice , Mice, Knockout , Promoter Regions, Genetic , Receptors, Adrenergic, beta-2/genetics , Receptors, Adrenergic, beta-2/metabolism , Receptors, Cell Surface/genetics , Receptors, Cell Surface/metabolism , Receptors, Corticotropin-Releasing Hormone/genetics , Receptors, Corticotropin-Releasing Hormone/metabolism , Receptors, Parathyroid Hormone/genetics , Receptors, Parathyroid Hormone/metabolism , Receptors, Thyrotropin/genetics , Receptors, Thyrotropin/metabolism , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Transfection
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