Effect of Dexmedetomidine Preconditioning on Hepatic Ischemia-Reperfusion Injury in Acute Hyperglycemic Rats.

BACKGROUND: Acute hyperglycemia frequently occurs in stressful situations, including liver transplantation or hepatic surgery, which may affect the protective effects of dexmedetomidine preconditioning and increase postoperative mortality. Therefore, this study aimed to investigate the effects of dexmedetomidine on hepatic ischemia-reperfusion injury in acute hyperglycemia. METHODS: Thirty-six Sprague-Dawley rats were randomly assigned to 6 groups, including a combination between 2 glycemic (normo- and hyperglycemia) and 3 ischemia-reperfusion conditions (sham, ischemia-reperfusion only, and dexmedetomidine plus ischemia-reperfusion). Dexmedetomidine 70 µg/kg was preconditioned 30 minutes before ischemic injury. After 6 hours of reperfusion, serum aminotransferase levels were measured to confirm the hepatic tissue injury. Furthermore, inflammatory (nuclear factor-κb, tumor necrosis factor-α, and interleukin-6) and oxidative stress markers (malondialdehyde and superoxide dismutase) were detected. RESULTS: Ischemia-reperfusion injury significantly increased the serum levels of aminotransferase and inflammatory and oxidative stress markers. These ischemia-reperfusion-induced changes were further exacerbated in hyperglycemia and were significantly attenuated by dexmedetomidine preconditioning. However, the effects of dexmedetomidine in hyperglycemia were lesser than those in normoglycemia (P < .05 for aminotransferases, inflammatory markers, malondialdehyde, and superoxide dismutase). CONCLUSIONS: These findings suggest that the protective effects of dexmedetomidine preconditioning may be intact against hepatic ischemia-reperfusion injury in acute hyperglycemia. Although its effects appeared to be relatively reduced, this may be because of the increase in oxidative stress and inflammatory response caused by acute hyperglycemia. To determine whether the effects of dexmedetomidine itself would be impaired in hyperglycemia, further study is needed.

Improved Image Analysis for Measuring Gastric Ulcer Index in Animal Models and Clinical Diagnostic Data.

Gastric ulcers are one of the most common gastrointestinal diseases. In this study, as an attempt to reduce the minimal error in clinical observations during the diagnosis of gastric ulcers, the applicability of improved ImageJ analysis (IA) was investigated by comparing the results of animal experiments and clinical data. As a result, IA exhibited a significantly improved potential for determining the ulcer index (UI) of clinical data sheets compared to those rated directly by conventional clinical observation (CCO). This indicated that IA enhanced the reproducibility of the measurement of gastric UI using a Bland-Altman plot, resulting in a reduced deviation of each UI value. In addition, it was confirmed that errors in gastric UI decisions can be reduced by adjusting RGB values in diagnostic clinical data (i.e., adjusting to 100 is relatively better than adjusting to 50 or 200). Together, these results suggest that the new enhanced IA could be compatible with novel applications for measuring and evaluating gastric ulcers in clinical settings, meaning that the developed method could be used not only as an auxiliary tool for CCO, but also as a pipeline for ulcer diagnosis.

Misinterpretation of carbon dioxide monitoring because of deadspace of heat and moisture exchanger with a filter in pediatric anesthesia: A case report.

RATIONALE: When patients are intubated and treated with mechanical ventilation, the upper respiratory tract is bypassed by the flow of dry and cold air. To prevent disturbances of airway homeostasis, a heat and moisture exchanger filter (HMEF) has been applied to breathing circuit. PATIENT CONCERNS: A 4-month-old male infant was ventilated with the pediatric HMEF. We report the impact of ignoring the direct influence of a filter containing deadspace in pediatric mechanical ventilation. DIAGNOSES: The breathing circuit with HMEF leads to unexpected complications such as mechanical obstructions owing to respiratory secretions, bleeding, inhaled drugs, and moisture. Besides these complications, we generally ignored the deadspace as the internal volume of the filters in breathing circuit for pediatric patients. INTERVENTIONS: After we noticed the influence of filter deadspace for pediatric patient, we removed the filter for effective respiratory circulation. OUTCOMES: The operation was completed without any specific incidents and the patient's voluntary breathing was well-maintained. The patient was discharged without any other complications. LESSONS: The increase in breathing apparatus deadspace should be minimized, and the clinicians should keep in mind that HMEF can causes respiratory acidosis with hypercapnia by apparatus deadspace rebreathing, especially for infants.

Analgesic effects of 1,2,3,4,6-penta-O-galloyl-ß-D-glucose in an animal model of lipopolysaccharide-induced pain.

We examined the analgesic effects of 1,2,3, 4,6-penta-O-galloyl-ß-D-glucose (ß-PGG), a prototypical gallotannin, in an animal model of lipopolysaccharide (LPS)­induced pain. To evaluate the analgesic activity of ß-PGG, we assessed the potential of ß-PGG to inhibit the generation of nitric oxide (NO) in LPS-stressed RAW 264.7 cells, and found that ß-PGG inhibits NO generation in a dose-dependent manner. Furthermore, the effects of ß-PGG on the voluntary movements of LPS-exposed animals were evaluated. The results showed that the voluntary movements of animals were markedly recovered after ß-PGG treatment. The mRNA expression of interleukin (IL)-1ß (1.33±0.38-fold) and IL-6 (0.64±0.40-fold) in the brain tissue of ß-PGG-treated animals markedly decreased compared with that observed in the control groups (3.86±0.91 and 2.45±1.12-fold, respectively) and in the other LPS-administered groups. The results showed that ß-PGG has potential to alleviate pain, not only by decreasing cellular NO generation in RAW 264.7 cells but also by the recovery of voluntary movement lost owing to inflammatory pain. This suggests that ß-PGG is comparable to ibuprofen, which was used as a positive control in this study. Collectively, these findings suggest that ß-PGG is a valuable natural compound which possesses analgesic activity.

The evaluation of implementing smart patient controlled analgesic pump with a different infusion rate for different time duration on postoperative pain management.

BACKGROUND: Control of postoperative pain is an important aspect of postoperative patient management. Among the methods of postoperative pain control, patient-controlled analgesia (PCA) has been the most commonly used. This study tested the convenience and safety of a PCA method in which the dose adjusted according to time. METHODS: This study included 100 patients who had previously undergone orthognathic surgery, discectomy, or total hip arthroplasty, and wished to control their postoperative pain through PCA. In the test group (n = 50), the rate of infusion was changed over time, while in the control group (n = 50), drugs were administered at a fixed rate. Patients' pain scores on the visual analogue scale, number of rescue analgesic infusions, side effects, and patients' satisfaction with analgesia were compared between the two groups. RESULTS: The patients and controls were matched for age, gender, height, weight, and body mass index. No significant difference in the mount of drug administered was found between the test and control groups at 0-24 h after the operation; however, a significant difference was observed at 24-48 h after the operation between the two groups. No difference was found in the postoperative pain score, number of side effects, and patient satisfaction between the two groups. CONCLUSIONS: Patient-controlled anesthesia administered at changing rates of infusion has similar numbers of side effects as infusion performed at a fixed rate; however, the former allows for efficient and safe management of postoperative pain even in small doses.

Erythropoietin prevents hypoxia-induced GATA-4 ubiquitination via phosphorylation of serine 105 of GATA-4.

Erythropoietin (EPO), an essential hormone for erythropoiesis, can provide protection against myocardial ischemia/reperfusion (I/R) injury and hypoxic apoptosis. GATA-4 is a zinc finger transcription factor, and its activation and post-translational modification are essential components in the transcriptional response to hypoxia. GATA-4 has also been reported to play a role in the cellular mechanisms of EPO-induced myocardial protection against I/R injury. In this study, we aimed to investigate the influence of EPO on GATA-4 protein stability and post-translational modification under hypoxic conditions without reperfusion. EPO induced cell viability under long-term hypoxia. EPO significantly increased phosphorylation of GATA-4 via the extracellular signal-regulated kinase (ERK) signaling pathway and reduced hypoxia-induced GATA-4 ubiquitination, which enhanced GATA-4 stability under hypoxia. ERK activation by over-expression of constitutively active mitogen-activated protein kinase 1 (MEK1) strongly increased GATA-4 phosphorylation and its protein levels and decreased GATA-4 ubiquitination under hypoxia. Despite ERK activation, GATA-4 ubiquitination was not affected under hypoxia in a GATA-4-S105A mutant. Under hypoxic condition without reperfusion, EPO-induced ERK activation was associated with post-translational modification of GATA-4, mediated by enhancement of phosphorylation of GATA-4 at Ser-105. Subsequent attenuation of GATA-4 ubiquitination led to increases in GATA-4 protein stability, which resulted in increased cell viability under hypoxia.

Berberine ameliorates cold and mechanical allodynia in a rat model of diabetic neuropathy.

This study evaluated the antiallodynic properties of berberine on cold and mechanical allodynia after streptozotocin (STZ)-induced diabetes using a rat model. Diabetic neuropathy was induced in rats by intraperitoneal injection of STZ. To measure cold and mechanical allodynia, a 4°C plate and von Frey filament were used, respectively. Cold and mechanical allodynia induced by diabetes were significantly decreased by single and repeated intraperitoneal treatment of amitriptyline at 10 mg/kg, and berberine at 10 and 20 mg/kg. The hepatic malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase activities were significantly increased in diabetic rats as compared with those in intact rats; however, in amitriptyline- and berberine-treated rats, they were significantly decreased as compared to the STZ control. The overall effects of berberine 20 mg/kg on cold and mechanical allodynia were quite similar to those of amitriptyline 10 mg/kg, and berberine exhibited similar antioxidant effects as the same dosage of amitriptyline. In conclusion, berberine (10 and 20 mg/kg) was observed to have antiallodynic effects against diabetes, which are presumed to be associated with antioxidative effects. It can be considered that the anti-inflammatory or antidepressant capacity of berberine could contribute to the antiallonynic effects shown in this study.

A comparison of femoral/sciatic nerve block with lateral femoral cutaneous nerve block and combined spinal epidural anesthesia for total knee replacement arthroplasty.

BACKGROUND: Several factors, such as compromised cardiopulmonary function, anticoagulative therapy, or anatomical deformity in the elderly, prevent general anesthesia and neuraxial blockade from being conducted for total knee replacement arthroplasty (TKRA). We investigated the efficacy of femoral/sciatic nerve block with lateral femoral cutaneous nerve block (FSNB) as an alternative procedure in comparison with combined spinal epidural nerve block (CSE) in patients undergoing TKRA. METHODS: In this observational study, 80 American Society of Anesthesiologists physical status I-III patients scheduled for elective unilateral TKRA underwent CSE (n = 40) or FSNB (n = 40). Perioperative side effects, intraoperative medications, duration and remaining amount of intravenous patient-controlled analgesia, rate of satisfaction with the surgical anesthesia and postoperative analgesia, willingness to recommend the same surgical anesthesia and postoperative analgesia to others, and postoperative visual analog scale pain scores were assessed. Statistical analysis was done using Chi-square test, Student's t-test, and repeated-measures analysis of variances. RESULTS: There was significantly more use of antihypertensives, analgesics, and sedatives in the FSNB group. There were no significant differences of perioperative side effects, duration and remaining amount of intravenous patient-controlled analgesia, rate of satisfaction with the surgical anesthesia and postoperative analgesia, willingness to recommend the same surgical anesthesia and postoperative analgesia to others, and postoperative visual analog scale scores between the two groups. CONCLUSIONS: FSNB with a sophisticated use of antihypertensives, analgesics, and sedatives to supplement insufficient block offers a practical alternative to CSE for TKRAs.

Moderate hypothermia attenuates α(1)-adrenoceptor-mediated contraction in isolated rat aorta: the role of the endothelium.

Moderate hypothermia (25-31 °C) may have a significant influence on vascular tone. We investigated the cellular mechanisms by which moderate hypothermia alters α-adrenoceptor-mediated contraction in rat thoracic aortae. Cyclooxygenase inhibition by indomethacin; nitric oxide (NO) synthase inhibition by L-NAME; potassium channel and endothelium-derived hyperpolarizing factor (EDHF) inhibition by glibenclamide and TEA; G protein inhibition by pertussis toxin; α2-adrenergic inhibition by yohimbine; and ß-adrenergic inhibition by propranolol were assessed for their effect on the contractile response to the α1-adrenoceptor agonist phenylephrine (Phe) in combination with moderate hypothermia (25 °C). Moderate hypothermia produced a shift to the right for the Phe concentration-response curves in endothelium-intact (E+) and endothelium-denuded (E-) aortic rings. The maximal response to Phe in E+ rings was significantly decreased (P<0.05) at 25 °C compared to 38 °C, whereas there was no significant difference in E- rings. Hypothermia-induced vasorelaxation in E+ rings was attenuated (P<0.05) following combined pretreatment with L-NAME (10⁻4 M) and indomethacin (10⁻5 M), whereas other inhibitors had no significant effect. Importantly, the addition of TEA to rings that were pretreated with L-NAME and indomethacin exhibited no further attenuation (P>0.05) of hypothermia-induced vasorelaxation. The concentrations of cGMP and cAMP, as measured by radioimmunoassay, were significantly increased (P<0.05) in E+ rings at 25 °C compared to those at 38 °C, whereas there were no significant differences (P>0.05) in E- rings. The present study demonstrated that rat aortic endothelium is stimulated during moderate hypothermia and that the NO-cGMP and prostacyclin (PGI2)-cAMP pathways represent endothelium-dependent mechanisms of hypothermia-induced vasorelaxation. In contrast, EDHF may not be associated with hypothermia-induced vasorelaxation.

The effect of the intravenous phenylephrine on the level of spinal anesthesia.

BACKGROUND: Spinal anesthesia causes hypotension and bradycardia due to sympathetic nerve block and it is difficult to predict the level of sensory block and the duration of blockade. Recent studies have reported that intravenous phenylephrine can reduce the rostral spread of spinal anesthesia in pregnant women. We think a phenylephrine infusion will be useful for maintaining the baseline blood pressure by reducing the rostral spread of spinal anesthesia during the elective surgery of non-obstetric patients. METHODS: SIXTY PATIENTS WHO WERE UNDERGOING UROLOGIC SURGERY WERE RANDOMIZED INTO TWO GROUPS: Group C (the control group without phenylephrine) and Group P (with the addition of phenylephrine). After a bolus infusion of 50 µg phenylephrine following the spinal injection, phenylephrine was continuously infused at the rate of 200 µg/hr. We compared the dermatomal spreads of spinal anesthesia, the hemodynamic parameters (blood pressure, heart rate) and the incidences of hypotension between the two groups. RESULTS: At 20 minutes, the level of the upper dermatome blocked against cold sensation was a median of T8 (interquartile range: T8-T10) for the phenylephrine group, as compared with T4 (interquartile range: T4-T6) for the control group (P < 0.001). CONCLUSIONS: Intravenous phenylephrine can decrease the rostral spread of spinal anesthesia during urologic surgery.

Target-controlled infusion of remifentanil for conscious sedation during spinal anesthesia.

BACKGROUND: The aim of this study was to define the optimal target concentration of remifentanil which effectively achieves conscious sedation without significant vital sign changes and side effects during spinal anesthesia. METHODS: Sixty patients underwent spinal anesthesia with 0.5% hyperbaric bupivacaine (8-16 mg), and were infused with a target controlled infusion (TCI) of remifentanil at 1.0 ng/ml (group R10, n = 15), 2.0 ng/ml (group R20, n = 15), 3.0 ng/ml (group R30, n = 15), and 3.5 ng/ml (group R35, n = 15). Observer's assessment of alertness/sedation (OAA/S) scale, the bispectral index (BIS), anxiety levels and infusion rate of remifentanil were monitored during the operation. RESULTS: OAA/S scale was significantly lower in groups R30 (3.96) and R35 (3.34) than groups R10 (4.31) and R20 (4.26). Incidence of intraoperative respiratory depression events, post operative nausea and vomiting were significantly higher in group R35 than the other groups. There were no significant differences in BIS, anxiety level and incidences of recall of the operative procedure among the groups. CONCLUSIONS: We conclude that the TCI of remifentanil at 3.0 ng/ml produces an effective sedation and anti-anxiety effects without significant side effects during spinal anesthesia.

Intravenous fentanyl during shoulder arthroscopic surgery in the sitting position after interscalene block increases the incidence of episodes of bradycardia hypotension.

BACKGROUND: Episodes of bradycardia hypotension (BH) or vasovagal syncope have a reported incidence of 13-29% during arthroscopic shoulder surgery in the sitting position after an interscalene block (ISB). This study was designed to investigate whether intravenous fentanyl during shoulder arthroscopy in the sitting position after ISB would increase or worsen the incidence of BH episodes. METHODS: In this prospective study, 20 minutes after being in a sitting position, 160 patients who underwent ISB were randomized to receive saline (S, n = 40), 50 µg of fentanyl (F-50, n = 40), 100 µg of fentanyl (F-100, n = 40) or 30 mg of ketorolac (K-30, n = 40) randomly. We assessed the incidence of BH episodes during the operation and the degree of maximal reduction (Rmax) of blood pressure (BP) and heart rate (HR). RESULTS: The incidence of BH episodes was 10%, 15%, 27.5% and 5% in the S, F-50, F-100 and K-30 groups, respectively. Mean Rmax of systolic BP in the F-100 group was significantly decreased as compared to the S group (-20.0 ± 4.5 versus -6.3 ± 1.6%, P = 0.004). Similarly, mean Rmax of diastolic BP in the F-100 group was also significantly decreased (P = 0.008) as compared to the S group. CONCLUSIONS: These results suggest that fentanyl can increase the incidence of BH episodes during shoulder arthroscopic surgery in the sitting position after ISB.

Reduction of matrix metalloproteinase-9 expression by culture filtrate of Paecilomyces farinosus J3.

The aim of the present study was to investigate the anti-tumor effects of a culture filtrate of Paecilomyces farinosus J3. Various anti-tumor assays using B16 melanoma cells were carried out. Paecilomyces farinosus J3 significantly decreased the wound healing capability, invasiveness and angiogenic activity, which was confirmed by wound healing, human umbilical vein endothelial cell and invasion assays. Paecilomyces farinosus J3 strongly inhibited cell migration, tube formation and the angiogenic process in a concentration-dependent manner. Zymographic analysis also indicated a reduced expression of matrix metalloproteinase-9 (MMP-9), a 92-kDa gelatinase. Taken together, the results indicate that the anti-tumor activities of Paecilomyces farinosus J3 originate from the reduction of MMP-9 expression in B16F10 cells.

Effect of pretreatment with acetaminophen on withdrawal movements associated with injection of rocuronium: a prospective, randomized, double-blind, placebo controlled study.

BACKGROUND: Withdrawal movement during rocuronium injection is a common, unresolved adverse effect. We aimed to investigate the effect of IV acetaminophen pretreatment on withdrawal movement during rocuronium injection. METHODS: This study enrolled 120 American Society of Anesthesiologists (ASA) I-II patients undergoing general anesthesia. They were randomly assigned to three treatment groups. After occluding venous drainage using a tourniquet on the upper arm, the saline group received 5 ml of 0.9% sodium chloride solution, the lidocaine group received 40 mg of lidocaine, and the acetaminophen group received 50 mg of acetaminophen. During injection of pretreatment drug, pain was assessed on a four-point scale. The tourniquet was released after 120 seconds and anesthesia was performed using thiopental sodium 5 mg/kg followed by rocuronium 0.6 mg/kg. The withdrawal movement was graded on a four-point scale in a double-blind manner. RESULTS: The incidence of pain on pretreatment injection in saline, lidocaine, and acetaminophen groups was 7.7%, 5.1%, and 2.5%, respectively. The incidence of withdrawal movements was 77.5% in saline group, 32.5% in lidocaine group, and 37.5% in acetaminophen group (P < 0.05). CONCLUSIONS: Acetaminophen and lidocaine reduced the incidence of withdrawal movement after rocuronium injection compared with saline.

Sympathetic block for treating primary erythromelalgia.

Primary erythromelalgia is a rare condition that's characterized by erythema, an increased skin temperature and burning pain in the extremities. The pain is often very severe, and treating erythromelalgia is frustrating and difficult. We report here on the case of a 12-year old girl with primary erythromelalgia in both lower extremities. The pain was refractory to medical treatment, but a bilateral sympathetic block with lidocaine and triamcinolone resulted in relief from the pain. Our experience with this disease demonstrates that sympathetic blocks are effective in improving the symptoms and they may be attempted on erythromelalgia patients who do not respond to other treatments, including medication and epidural blocks.

Anesthesia of a dental patient with Angelman syndrome -A case report-.

Angelman syndrome is characterized by a partial deficit of paired autosomal chromosome 15, which contains a subunit of the GABA (Gamma-Amino Butyric Acid) receptor. Many drugs that act on the CNS (Central Nerve System) during anesthesia are believed to exert their effects via the GABA receptors. We describe the anesthesia of a 7 year-old female patient with Angelman syndrome who underwent surgery for dental caries. The basic factors that needed to be considered when administering anesthesia to this patient were epilepsy, significant dominance of the vagal tone, craniofacial abnormalities and peripheral muscular atrophy. Inhalational anesthetics (sevoflurane) were employed for this patient. The patient had an uneventful peri-operative period and was discharged home on the same day of the operation.

Amelioration of asthmatic inflammation by an aqueous extract of Spinacia oleracea Linn.

Inflammation of the respiratory tract is a crucial process in immune diseases, including asthma, and atopic rhinitis. To establish whether an aqueous extract of Spinacia oleracea Linn (SoL) has a beneficial influence in terms of anti-asthmatic activity, we examined its effects on an ovalbumin-induced asthmatic model. Mice sensitized to ovalbumin were orally administered the SoL extract, and their lungs examined by hematoxylin and eosin staining to determine IL-4/13 cytokine expression. The SoL extract exerted strong anti-asthmatic effects by inducing a decrease in the CD4+ cell number, IL-4/13, and other molecular markers in the lung. Our results collectively indicate that the aqueous SoL extract ameliorates asthmatic symptoms effectively in a mouse ovalbumin-challenge model.

Contralateral allodynia and central change in the chronic post-ischemic pain model rats.

BACKGROUND: Mirror-image allodynia is a mysterious phenomenon that occurs in association with many clinical pain syndromes including complex regional pain syndromes (CRPS). Underlying mechanisms for the development of such pain are still a matter of investigation. Several studies suggest that activation of the N-methyl-D-aspartate (NMDA) receptor is essential for central sensitization as a base for persistent pain. The aim is to assess whether alteration of NMDA receptor expression correlates with the contralateral allodynia in the chronic post-ischemia pain (CPIP) model rats representing CRPS-Type I. METHODS: Application of a tight-fitting tourniquet for a period of 3 hours before reperfusion produced CPIP in male Sprague-Dawley rats. The mechanical paw withdrawal thresholds to von Frey stimuli (using a dynamic plantar aesthesiometer) were measured as pain indicators in ipsilateral and contralateral hindpaws. Phosphorylation of the NMDA receptor 1 subunit (pNR1), assessed with Western blot, was measured in the contralateral L4-6 spinal cord. RESULTS: Ipsilateral and contralateral mechanical allodynia is present at 4 hours after reperfusion, peaked at 3 days, and continued for 7 days after reperfusion. The relative density of pNR1 of CPIP rats significantly decreased in the contralateral L4-6 spinal cord compared to baseline value (P < 0.05). There was significant correlation between paw withdrawal threshold and the relative density of pNR1 (ipsilateral; R2 = 0.75, P < 0.01, contralateral; R2 = 0.60, P < 0.01). CONCLUSIONS: These data suggest that pNR1 is correlated to the contralateral mechanical allodynia in CPIP rats.

Prophylactic antiemetic effect of midazolam after middle ear surgery.

OBJECTIVE: To investigate the prophylactic antiemetic effect of midazolam after middle ear surgery. STUDY DESIGN: A prospective, randomized, double-blind, placebo-controlled study. SUBJECTS AND METHODS: Ninety women patients undergoing middle ear surgery with general anesthesia received intravenously either midazolam 0.075 mg/kg or normal saline (n = 45 each) after induction of anesthesia. The incidence and severity of postoperative nausea and vomiting, rescue antiemetics, pain intensity, and side effects such as headache, dizziness, and drowsiness were assessed during the first 24 hours after anesthesia. RESULTS: Midazolam groups showed total incidence and severity of nausea and vomiting. Patients who required rescue antiemetics were significantly lower than in saline group (P < 0.05), but there were no significant differences in pain intensity and side effects such as headache, dizziness, and drowsiness between groups. CONCLUSIONS: Midazolam 0.075 mg/kg is effective for reducing nausea and vomiting after middle ear surgery.