The Anti-Inflammatory and Antioxidant Effects of Propofol and Sevoflurane in Children With Cyanotic Congenital Heart Disease.

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.

Long-Term Disease Prevention with a Gene Therapy Targeting Oligodendrocytes in a Mouse Model of Adrenomyeloneuropathy.

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.

Correction of a knock-in mouse model of acrodysostosis with gene therapy using a rAAV9-CAG-human PRKAR1A vector.

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.

Effect of One-Lung Ventilation on Blood Sevoflurane and Desflurane Concentrations.

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.

[Remifentanil-ketamine vs. propofol-ketamine for sedation in pediatric patients undergoing colonoscopy: A randomized clinical trial]. / Remifentanil­cetamina vs. propofol­cetamina para sedação em pacientes pediátricos submetidos à colonoscopia: ensaio clínico randômico.

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.

Comparative study of ultrasound-guided paravertebral block versus intravenous tramadol for postoperative pain control in percutaneous nephrolithotomy.

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.

Comparison of the cardioprotective effects of dexmedetomidineand remifentanil in cardiac surgery

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.

[Effect of rocuronium administration rate and remifentanil on prevention of rocuronium injection pain in pediatric cases]. / Pediyatrik olgularda roküronyum enjeksiyon agrisinin azaltilmasinda roküronyum uygulama hizi ve remifentanilin etkisi.

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.

Preoperative informational video reduces preoperative anxiety and postoperative negative behavioral changes in children.

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.

The IGF1 P2 promoter is an epigenetic QTL for circulating IGF1 and human growth.

BACKGROUND: Even if genetics play an important role, individual variation in stature remains unexplained at the molecular level. Indeed, genome-wide association study (GWAS) have revealed hundreds of variants that contribute to the variability of height but could explain only a limited part of it, and no single variant accounts for more than 0.3% of height variance. At the interface of genetics and environment, epigenetics contributes to phenotypic diversity. Quantifying the impact of epigenetic variation on quantitative traits, an emerging challenge in humans, has not been attempted for height. Since insulin-like growth factor 1 (IGF1) controls postnatal growth, we tested whether the CG methylation of the two promoters (P1 and P2) of the IGF1 gene is a potential epigenetic contributor to the individual variation in circulating IGF1 and stature in growing children. RESULTS: Child height was closely correlated with serum IGF1. The methylation of a cluster of six CGs located within the proximal part of the IGF1 P2 promoter showed a strong negative association with serum IGF1 and growth. The highest association was for CG-137 methylation, which contributed 13% to the variance of height and 10% to serum IGF1. CG methylation (studied in children undergoing surgery) was approximately 50% lower in liver and growth plates, indicating that the IGF1 promoters are tissue-differentially methylated regions (t-DMR). CG methylation was inversely correlated with the transcriptional activity of the P2 promoter in mononuclear blood cells and in transfection experiments, suggesting that the observed association of methylation with the studied traits reflects true biological causality. CONCLUSIONS: Our observations introduce epigenetics among the individual determinants of child growth and serum IGF1. The P2 promoter of the IGF1 gene is the first epigenetic quantitative trait locus (QTL(epi)) reported in humans. The CG methylation of the P2 promoter takes place among the multifactorial factors explaining the variation in human stature.

Comparison between minimal right vertical infra-axillary thoracotomy and standard median sternotomy for repair of atrial septal defects.

BACKGROUND: The minimal right vertical infra-axillary thoracotomy could be a safe and cosmetic alternative to standard median sternotomy. This study reviews our results and experience with a minimal right vertical infra-axillary thoracotomy technique for the repair of atrial septal defects compared with standard median sternotomy. METHODS: The study was designed as a retrospective, observational, and case-controlled study. Between May 2007 and November 2012, 26 patients underwent atrial septal defect closure with standard median sternotomy (Group 1). This group was compared with 21 patients who underwent repair of atrial septal defects using minimal right vertical infra-axillary thoracotomy (Group 2). Quantitative data were given as mean ± standard deviation, and qualitative values were expressed as percentages. In the comparison of the normal variables between the two groups, we used independent sample t test, and in the comparison of categorical variables between groups, Chi-square test was used. RESULTS: The mean length of incision was significantly shorter in Group 2 than in Group 1 (p = 0.03). The time it took to establish cardiopulmonary bypass was longer in Group 2 (p = 0.04). There were no statistically significant differences in cardiopulmonary bypass time (p = 0.11), aortic cross-clamp time (p = 0.10), and total operation time (p = 0.10) between the two groups. Group 2 had less chest tube drainage (p = 0.04), less blood transfusion (p = 0.02), and shorter postoperative mechanical ventilation time (p = 0.09) than Group 1. CONCLUSION: Minimal right vertical infra-axillary thoracotomy can be performed with favorable cosmetic and clinical results for atrial septal defects closure. Infra-axillary thoracotomy provides a good alternative to standard median sternotomy for patients with atrial septal defects.

The Effect of Intravenous Magnesium Sulphate Treatment on the Spinal Anaesthesia Produced by Bupivacaine in Pre-eclamptic Patients.

OBJECTIVE: In our study, the effect of intravenous magnesium sulphate in normal and pre-eclamptic patients on spinal anaesthesia produced by bupivacaine was investigated. METHODS: Sixty-four pregnant (32 normal and 32 pre-eclamptic) were accepted in this study. Pregnants were divided into four groups as patients given intravenous magnesium sulphate and as control. Spinal anaesthesia was induced with 12.5 mg 0.5% hyperbaric bupivacaine. Intraoperative and postoperative haemodynamic variables, sensorial block periods, onset times of sensorial and motor block, maximum sensorial block levels, the time to reach maximum block level, Bromage scores, consumptions of intraoperative analgesic and ephedrine, the quality of anaesthesia, the duration of spinal anaesthesia and magnesium levels in blood and cerebrospinal fluid were measured and recorded. RESULTS: The level of magnesium in blood and cerebrospinal fluid was significantly higher in the group given magnesium in pre-eclamptic patients (p<0.01). Onset of sensory block times were significantly longer in intravenous magnesium group than in groups 1, 2 and 3 (p<0.05). Onset of motor block times were significantly longer and the duration of anaesthesia was shorter in groups given magnesium (p<0.05). Although the quality of anaesthesia was similar, supplemental analgesic consumption was significantly higher in pre-eclamptic pregnants given magnesium sulphate than in pre-eclamptic pregnants who were not given magnesium sulphate (p<0.05). CONCLUSION: Intravenous magnesium sulphate treatment during the spinal anaesthesia produced by bupivacaine extended the onset of sensory and motor block times, shortened the duration of spinal anaesthesia and therefore led to early analgesic requirement.

Vitamin D and Anaesthesia.

Vitamin D is a vitamin not only associated with calcium-phosphorus metabolism but also affects many organ systems. Because of its effect on the immune system in recent years, it has attracted much attention. Vitamin D deficiency is a clinical condition that can be widely observed in the society. Thus, patients with vitamin D deficiency are often seen in anaesthesia practice. In the absence of vitamin D, prolongation of intensive care unit stay, increase in mortality and morbidity and also association of chronic diseases further increase the importance of vitamin D deficiency. The results obtained from studies have led to the question of whether poor surgical outcome is associated with vitamin D deficiency. We assessed the vitamin D deficiency and its negative consequences for the anaesthesiologist.

Effect of Ketamine, Thiopental and Ketamine-Thiopental Combination during Electroconvulsive Therapy for Depression.

OBJECTIVE: We aimed to evaluate the effect of anaesthesia with thiopental (4 mg kg(-1)), ketamine (1 mg kg(-1)) and ketamine-thiopental (1 mg kg(-1) and 4 mg kg(-1), respectively) combination during electroconvulsive therapy (ECT) on the Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HAM-A) and haemodynamic variables in patients with resistant major depression. METHODS: Patients with HDRS scores above 17 were included. The patients were randomly divided into three groups according to the anaesthesia used. Group 1 was given thiopental (4 mg kg(-1)), Group 2 was given ketamine (1 mg kg(-1)) and Group 3 was given ketamine (1 mg kg(-1)) and thiopental (4 mg kg(-1)). Succinylcholine (1 mg kg(-1)) was administered in all patients for muscle relaxation. HDRS and HAM-A scores were evaluated before ECT, after 3, 6. ECT and after the final ECT. Systolic and diastolic blood pressures, heart rates and oxygen saturations were recorded before and after anaesthesia induction and after the ECT procedure. Seizure duration was recorded. RESULTS: Fifty-eight patients were included in the study. Thirty (52%) patients were male and 28 (48%) were female. The mean age was 42.7±15.8 years in Group 1, 44.8±11 years in Group 2 and 38.6±6.8 years in Group 3. In all groups, HDRS scores were reduced compared with the baseline values. There was no statistical significant difference between the groups regarding HDRS scores. HAM-A scores were higher in Group 2 and Group 3. Systolic and diastolic blood pressures and heart rate values were lower in Group 1 and the difference was statistically significant. CONCLUSION: In this study, anaesthesia induced with thiopental, ketamine and thiopental-ketamine combination was observed to not result in a difference in ECT for patients with treatment-resistant depression. Ketamine at a dose of 1 mg kg(-1) given just before ECT did not enhance the antidepressant effect of ECT; however, anxiety scores were increased with ketamine application.

Preventive and therapeutic effects of a beta adrenoreceptor agonist, dobutamine, in carrageenan-induced inflammatory nociception in rats.

We hypothesized that locally administrated ß-adrenoreceptor agonist can modulate the inflammatory nociceptive parameters in carrageenan (CG)-induced peripheral inflammatory pain. This study was therefore aimed to assess the preventive and therapeutic effects of a ß-agonist, dobutamine, by investigating its pretreatment and posttreatment actions on the inflammation-induced hypersensitivities (thermal hyperalgesia, mechanical allodynia) to cutaneous stimulation, edema, and several biochemical oxidant and anti-oxidant parameters in a rat model of CG-induced hind paw inflammation. Effects of dobutamine were compared with those of esmolol, a ß-adrenoreceptor antagonist. CG injection to healthy rats lowered the thermal latencies (from 10.1 ± 0.2 to 4.9 ± 0.1 s) and mechanical thresholds (from 32.9 ± 0.5 to 18.9 ± 1.3 g) and caused the hyperalgesia and allodynia. In CG-induced inflamed paws, while intraplantar esmolol treatment (1 mg) produced significant decreases in latencies (4.1 ± 0.1 s) and thresholds (15.2 ± 2.4 g), dobutamine (1 mg) increased the latencies (11.3 ± 0.5 s) and thresholds (26.3 ± 2.8 g). In contrast to esmolol, dobutamine increased the superoxide dismutase level and decreased the myeloperoxidase, malondialdehyde, and nitric oxide levels in CG-induced inflamed paws. The present results can reveal that ß-adrenoreceptors may play a role in inflammatory nociceptive processes, and locally treated ß-adrenoreceptor agonists such as dobutamine can be a preferable, appropriate choice for the management of inflammatory nociception due to their preventive and therapeutic effects on CG-induced peripheral inflammatory nociception.

Anaesthetic Management of a Patient with Hereditary Angioedema.

Hereditary angioedema (HAE) is a rare autosomal dominant disorder caused by reduced activity of the C1 esterase inhibitor. Clinically, angioedema most often involves the upper extremities, face, neck and larynx. The most common cause of death is asphyxia related to laryngeal oedema. Attacks are triggered by many factors such as trauma, stress, infections and hormonal fluctuations. C1 esterase inhibitor concentrates, fresh frozen plasma (FFP), androgen steroids, quinine pathway inhibitors and antifibrinolytics can be used as treatment. In this case report, the anaesthetic management of a patient with hereditary angioedema undergoing laminectomy surgery is reported.

Dexmedetomidine modifies uterine contractions in pregnancy terms of rats.

OBJECTIVES: The present study was aimed at determining the effective doses of Dexmedetomidine (Dex) involved in amplitude of contraction-force and frequency of uterine rings in pregnancy terms of rats. All experiments involving animal subjects were carried out with the approval of animal care and use Ethical Committee of Cukurova University. Experiments were performed on female Albino-Wistar rats (200-260 g; n = 40). MATERIALS AND METHODS: Uterine rings from pregnant rats were placed in organ bath with Krebs and calcium ion (Ca(2+))-free solutions to record and exposed to serially increasing log10 concentrations of Dex. RESULTS: In Krebs solution, while Dex caused an increase in the spontaneous contraction-forces in all pregnancy terms of rats in a significant dose-dependent manner, it led to a decrease in contraction-frequency in late-pregnancy term of rats. In Ca(2+)-free, the spontaneous contraction-force decreased in late-pregnancy term and increased in early and middle-pregnancy terms. In addition, while Dex increased the contraction-frequency in early and middle-pregnancy terms, it decreased in late-pregnancy term in a dose-dependent manner. STATISTICAL ANALYSIS USED: The data were subjected to one-way analysis of variance. Repeated measures were employed for comparison of several group means through the Tukey post-hoc test (SPSS 10.00 Inc., Chicago, Ill, USA). P < 0.05 was considered statistically significant. CONCLUSIONS: This study suggested that Dex might differently alter the spontaneous contraction-forces and contraction-frequencies of uterine rings in all pregnancy terms of rats in Krebs and Ca(2+)-free solutions.

Comparison of actions of systemically and locally administrated local anaesthetics in diabetic rats with painful neuropathy.

Nothing is known about actions of levobupivacaine, a long-acting local anaesthetic belonging to the amino amide group, in diabetes-induced neuropathic pain conditions. In this study, we therefore investigated the possible antihyperalgesic and antiallodynic effects of levobupivacaine in diabetic animal model. Actions of systemically (intraperitoneal) or locally (intraplantar) administrated levobupivacaine on streptozotocin-induced diabetic rats with painful neuropathy were examined using a thermal plantar test and a dynamic plantar aesthesiometer. Effects of levobupivacaine were compared with those of a well-known amide local anaesthetic lidocaine. Levobupivacaine was more potent than lidocaine in all tests employed on diabetic rats. After intraperitoneal injections to diabetic rats, levobupivacaine, but not lidocaine, produced pronounced antihyperalgesic and antiallodynic effects. However, intraplantar administration of both levobupivacaine and lidocaine produced antihyperalgesic and antiallodynic action in diabetic rats. In contrast to the transient effects of lidocaine (30 min), antihyperalgesic and antiallodynic actions of levobupivacaine gradually disappeared within 120 min after intraplantar injections. Intraperitoneal or intraplantar administrations of levobupivacaine or lidocaine at the effective dose had no effect on any parameters in intact rats. Findings revealed that antiallodynic and antihyperalgesic potency of levobupivacaine was higher in comparison with that of lidocaine after their intraperitoneal or intraplantar administration to diabetic animals. Furthermore, locally administrated levobupivacaine has the greatest antihyperalgesic and antiallodynic actions in diabetic rats.

PRKAR1A and PDE4D mutations cause acrodysostosis but two distinct syndromes with or without GPCR-signaling hormone resistance.

CONTEXT: Acrodysostosis is a rare skeletal dysplasia that is associated with multiple resistance to G protein-coupled receptor (GPCR) signaling hormones in a subset of patients. Acrodysostosis is genetically heterogeneous because it results from heterozygous mutations in PRKAR1A or PDE4D, two key actors in the GPCR-cAMP-protein kinase A pathway. OBJECTIVE: Our objective was to identify the phenotypic features that distinguish the two genotypes causing acrodysostosis. PATIENTS AND METHODS: Sixteen unrelated patients with acrodysostosis underwent a candidate-gene approach and were investigated for phenotypic features. RESULTS: All patients had heterozygous de novo mutations. Fourteen patients carried a PRKAR1A mutation (PRKAR1A patients), five each a novel PRKAR1A mutation (p.Q285R, p.G289E, p.A328V, p.R335L, or p.Q372X), nine the reported PRKAR1A p.R368X mutation; two patients harbored a mutation in PDE4D (PDE4D patients) (one novel mutation, p.A227S; one reported, p.E590A). All PRKAR1A, but none of the PDE4D mutated patients were resistant to PTH and TSH. Two PRKAR1A patients each with a novel mutation presented a specific pattern of brachydactyly. One PDE4D patient presented with acroskyphodysplasia. Additional phenotypic differences included mental retardation in PDE4D patients. In addition, we report the presence of pigmented skin lesions in PRKAR1A and PDE4D patients, a feature not yet described in the acrodysostosis entity. CONCLUSIONS: All PRKAR1A and PDE4D patients present similar bone dysplasia characterizing acrodysostosis. Phenotypic differences, including the presence of resistance to GPCR-cAMP signaling hormones in PRKAR1A but not PDE4D patients, indicate phenotype-genotype correlations and highlight the specific contributions of PRKAR1A and PDE4D in cAMP signaling in different tissues.

Antinociceptive activities of lidocaine and the nav1.8 blocker a803467 in diabetic rats.

The streptozocin-induced diabetic rat is a model of chronic pain that shows signs of hyperalgesia and allodynia and may replicate signs in diabetic humans. Here we investigated the antinociceptive effects of A803467, a highly selective blocker of Nav1.8 channels, in diabetic rats with painful neuropathy. We systemically (intraperitoneal) or locally (intraplantar) administered A803467 (or lidocaine, a nonselective sodium channel blocker, as a control) to diabetic rats with hyperalgesia and allodynia and then measured thermal latencies and mechanical thresholds. With intraperitoneal administration, A803467 led to 6-fold greater reduction of hyperalgesia and 2-fold greater reduction of allodynia than did lidocaine. Whereas the antihyperalgesic effects of lidocaine and A803467 were similar after intraplantar administration, A803467 (1 mg) was at least 2 times more effective as an antiallodynic than was lidocaine (0.5 mg). These results suggest that compared with lidocaine, systemic or local blockade of Nav1.8 channels by A803467 may more effectively relieve hyperalgesia and allodynia in diabetic neuropathy.