Inhibition of Oxidative Stress in Renal Ischemia-Reperfusion Injury.

BACKGROUND: Superoxide, nitric oxide (NO), and peroxynitrite are important mediators in the pathogenesis of ischemia-reperfusion (I/R) injury. We tested the renoprotective effects of allopurinol (ALP), a xanthine oxidase inhibitor, N-nitro-L-arginine methyl ester (L-NAME), and 5,10,15,20-tetrakis (N-methyl-4-pyridyl) porphyrinato iron (III) (FeTMPyP) by selective inhibition of superoxide, NO, and peroxynitrite, respectively. METHODS: Male Sprague-Dawley rats were randomly assigned to 5 groups (n = 6 per group). Group 1 was a sham-operated group. Group 2 was the renal I/R group (30-minute ischemia followed by 24-hour reperfusion). Rats in groups 3, 4, and 5 received ALP, L-NAME, or FeTMPyP, respectively, at 5 minutes before the reperfusion. Serum creatinine (Cr), blood urea nitrogen (BUN), renal tissue malondialdehyde, superoxide dismutase, histological changes, apoptosis, and monocyte infiltration were evaluated. In addition, the combined treatment with ALP and L-NAME was compared with FeTMPyP in a second independent experiment. RESULTS: The administration of ALP, L-NAME, and FeTMPyP diminished the increase in Cr (P = .0066 for all) and BUN (P = .0066 for ALP; and P = .013 for L-NAME) induced by I/R injury and decreased the histological damage (P = .0066 for all). In addition, ALP, L-NAME, and FeTMPyP attenuated the oxidative stress response as determined by a decrease in malondialdehyde level (P = .0066 for all), apoptotic renal tubular cells (P = .0066 for all), and monocyte infiltration (P = .0066 for all). The combined treatment of ALP and L-NAME decreased Cr and BUN levels to a greater degree than FeTMPyP (P = .016 for Cr; P = .0079 for BUN). CONCLUSIONS: Superoxide, NO, and peroxynitrite are involved in renal I/R injury. The reduction of peroxynitrite formation, via inhibition of superoxide or NO, or the induction of peroxynitrite decomposition may be beneficial in renal I/R injury.

Curcumin could prevent the development of chronic neuropathic pain in rats with peripheral nerve injury.

BACKGROUND: Peripheral nerve injury results in chronic neuropathic pain characterized by allodynia and/or spontaneous pain. It has been suggested that activation of mitogen-activated protein kinases such as extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) contribute to the neuropathic pain. OBJECTIVES: We investigated if curcumin could prevent the development of neuropathic pain in rats with chronic constriction injury (CCI) of the sciatic nerve. METHODS: The animals were divided into 3 groups. In the curcumin treatment group (n = 10), curcumin (50 mg/kg/d PO) was administered once daily from 1 day before CCI to 7 days after CCI. The rats in the sham group (n = 10) and CCI group (n = 10) received a control vehicle. The mechanical allodynia was assessed using von Frey at 1, 3, 5, and 7 days after nerve injury. Western blots were used to evaluate the levels of p-ERK, p-JNK, and phosphorylation of NR1 (p-NR1) subunits of N-methyl-D-aspartate in the spinal dorsal root ganglion. RESULTS: In the CCI group, mechanical allodynia was observed during 7 days after nerve injury. However, curcumin treatment reversed the mechanical allodynia 7 days after nerve ligation. There were no differences in the expression of p-ERK, p-JNK, and p-NR1 between the sham and curcumin groups. However, the expression of p-ERK, p-JNK, and p-NR1 in the CCI group were higher than the sham group and curcumin group, respectively (P < 0.05). CONCLUSIONS: Treatment with curcumin during the early stages of peripheral neuropathy can prevent the development of chronic neuropathic pain.

Suspected Malignant Hyperthermia in a Brain-Dead Donor During Anesthesia for Organ Procurement Surgery: A Case Report.

We report an unusual case of highly suspected malignant hyperthermia after inducing anesthesia in a brain-dead 18-year-old male patient undergoing organ procurement surgery. The patient was administered desflurane (3 vol%) and rocuronium bromide (50 mg) to induce and maintain general anesthesia. He experienced hypercapnia and tachycardia within 5 minutes of anesthesia induction; however, his body temperature rapidly rose only after 15 minutes. The volatile anesthetic was discontinued, and dantrolene was administered at a low dose (1 mg/kg) to avert possible hepatotoxic effects on the donor liver. Fortunately, the clinical course of the brain-dead donor until the organs were harvested and the liver transplantation outcome of the recipient was favorable. A comprehensive understanding of the pathophysiology of brain death, organ transplantation, and malignant hyperthermia is essential to respond promptly and appropriately. Based on our experience, low-dose dantrolene may be clinically used in brain-dead donors while accounting for its potential hepatotoxic effects.

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.

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.

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.

The Role of Dexmedetomidine in Hepatic Ischemia-Reperfusion Injury Via a Nitric Oxide-Dependent Mechanism in Rats.

BACKGROUND: Dexmedetomidine is known to protect against ischemia-reperfusion (IR) in various organs; however, the mechanisms of dexmedetomidine in the liver remain unclear. We investigated whether dexmedetomidine preconditioning leads to hepatic protection and whether nitric oxide was associated with this protective mechanism by employing N-nitro-l-arginine methyl ester (l-NAME), a nitrous oxide synthase inhibitor. METHODS: Experiment 1 included 24 rats in 4 groups: sham, IR, 30 µg/kg of dexmedetomidine, and 50 µg/kg of dexmedetomidine. Experiment 2 included 36 rats in 6 groups: IR, 50 µg/kg of dexmedetomidine, 10 mg/kg of l-NAME, 10 mg/kg of l-NAME + 50 µg/kg of dexmedetomidine, 30 of mg/kg l-NAME, and 30 mg/kg of l-NAME + 50 µg/kg of dexmedetomidine. All drugs were administered intraperitoneally. The levels of serum transaminases, malondialdehyde, superoxide dismutase, tumor necrosis factor-α, nuclear factor-κB, and c-Jun N-terminal kinase were measured 6 hours after hepatic surgery. RESULTS: Dexmedetomidine demonstrated a dose-dependent decrease in serum transaminase levels. The 50-µg/kg dexmedetomidine group showed a significant decrease in malondialdehyde levels (P = .002), increase in superoxide dismutase levels (P = .002), and a significantly lower level of phosphorylated tumor necrosis factor-α, nuclear factor-κB, and c-Jun N-terminal kinase (P = .002, respectively) compared with the IR injury group. These protective effects of dexmedetomidine were partially reversed by pretreatment with l-NAME (P < .01 for 20 and 30 mg/kg of l-NAME). CONCLUSION: In hepatic IR injury, dexmedetomidine might protect the liver via antioxidative and anti-inflammatory responses, and nitric oxide production could play a role in these protective mechanisms.

Antiemetic effects of midazolam added to fentanyl-ropivacaine patient-controlled epidural analgesia after subtotal gastrectomy: A prospective, randomized, double-blind, controlled trial.

BACKGROUND: Nausea and vomiting are frequent adverse effects of patient-controlled epidural analgesia (PCEA) with opioids. OBJECTIVE: This study was designed to assess the antiemetic effect of midazolam added to fentanyl-ropivacaine PCEA. METHODS: In a prospective, randomized, double-blind, controlled trial, smoking patients with gastric cancer undergoing elective subtotal gastrectomy were evenly allocated to 1 of 2 treatment groups to manage postoperative pain: 0.2% ropivacaine mixed with fentanyl 4 µg/mL and midazolam 0.2 mg/mL (test group) or 0.2% ropivacaine mixed with fentanyl 4 µg/mL (control group). The PCEA infusion was set to deliver 4 µL/h of the study solution, with a bolus of 2 mL per demand and a 15-minute lockout time. The incidence of postoperative nausea and vomiting (PONV), pain intensity, sedation score, usage of rescue analgesia and rescue antiemetic, respiratory depression, urinary retention, and pruritus were recorded at 2, 6, 12, 24, 48, and 72 hours after surgery. Total infused volume of PCEA at 72 hours after surgery was measured. RESULTS: A total of 60 patients were approached and randomized to treatment. No patients were excluded by exclusion criteria and all enrolled patients completed this study. Incidence of nausea (7% vs 33%; P = 0.02) in the test group was significantly lower than in the control group. The overall frequency of PONV in the test group was significantly less than that of the control group (7% vs 40%; P = 0.006). In addition, the mean (SD) infused volume of PCEA in the test group was significantly lower than that in the control group (392.3 [68.9] vs 351.2 [49.8] mL; P = 0.01). However, there were no significant differences in pain intensity, usage of rescue antiemetics and rescue analgesics, and mild pruritus between groups. No patient reported moderate or severe sedation, respiratory depression, or hypoxemia. In addition, there were no severe adverse events. CONCLUSIONS: Midazolam added to fentanyl-ropivacaine PCEA was associated with a significant reduction in the incidence of PONV compared with fentanyl-ropivacaine alone, and a significant decrease in the amount of PCEA administered without a significant increase in adverse events in these patients who underwent subtotal gastrectomy.

Comparison of Whitacre needle and Chiba needle on the incidence of intravascular injection during caudal epidural injections: A single-blind, randomized clinical consort study.

ABSTRACT: Caudal epidural injection (CEI) is effective for lumbar spinal pain. However, accidental intravascular injection reduces therapeutic efficacy of CEI and leads to fatal complications such as hematoma, and neurologic deficit. Whitacre needle has been reported to be effective for reducing intravascular injection during transforaminal epidural injection, compared with Quincke needle. The bevel of Chiba needle is shorter than that of Quincke needle. In this study we compared Whitacre needle and Chiba needle on incidence of intravascular injection during CEI.This was a single-blind, randomized clinical consort study. After institutional Review Board approval, a total of 164 patients underwent CEI were randomly allocated to one of 2 group (Whitacre needle or Chiba needle group). Intravascular injection was assessed with real-time fluoroscopy. In addition, total procedure time was measured. Data were compared between groups, and P < .05 was consideredstatistically significant.There were no differences between groups in terms of patient demographic and clinical characteristics. There was no significant difference on incidence of intravascular injection between Whitacre and Chiba needle group (11% vs 19.5%, P = .192). However, the procedure time is significantly longer in the Whitacre than Chiba needle group (172.8 ±â€Š53.8 sec vs 147.1 ±â€Š61.1 sec, P = .005).Based on current study, our results indicated that Whitacre needle was not effective to decrease the incidence of intravascular injection during CEI, compared to Chiba needle.

The Effect of Nitric Oxide on Remote Ischemic Preconditioning in Renal Ischemia Reperfusion Injury in Rats.

Although remote ischemic preconditioning (RIPC) is an organ-protective maneuver from subsequent ischemia reperfusion injury (IRI) by application of brief ischemia and reperfusion to other organs, its mechanism remains unclear. However, it is known that RIPC reduces the heart, brain, and liver IRI, and that nitric oxide (NO) is involved in the mechanism of this effect. To identify the role of NO in the protective effect of RIPC in renal IRI, this study examined renal function, oxidative status, and histopathological changes using N-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor. Remote ischemic preconditioning was produced by 3 cycles of 5 minutes ischemia and 5 minutes reperfusion. Blood urea nitrogen, creatinine (Cr), and renal tissue malondialdehyde levels were lower, histopathological damage was less severe, and superoxide dismutase level was higher in the RIPC + IRI group than in the IRI group. The renoprotective effect was reversed by L-NAME. Obtained results suggest that RIPC before renal IRI contributes to improvement of renal function, increases antioxidative marker levels, and decreases oxidative stress marker levels and histopathological damage. Moreover, NO is likely to play an important role in this protective effect of RIPC on renal IRI.

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.

A combination of lidocaine (lignocaine) and remifentanil reduces pain during propofol injection.

OBJECTIVE: Pain on injection is a well known adverse effect of propofol. The purpose of this study was to compare the analgesic effect of a lidocaine (lignocaine)/remifentanil combination compared with either lidocaine alone or remifentanil alone during propofol injection for induction of anaesthesia. METHODS: In a randomised, double-blind, prospective trial, 129 patients were allocated to one of three groups (each n = 43) receiving lidocaine 20mg, remifentanil 0.3 microg/kg or lidocaine 20 mg plus remifentanil 0.3 microg/kg as pretreatment, followed by injection of 5 mL of 1% propofol. Pain severity was evaluated on a four-point scale. RESULTS: Two patients (4.7%) complained of pain in the lidocaine plus remifentanil group compared with 15 (35.7%) in the lidocaine alone group and 18 (42.9%) in the remifentanil alone group (p < 0.001). There was no significant difference in the incidence of injection pain between the lidocaine alone and remifentanil alone groups (p = 0.21). CONCLUSION: Pretreatment with a combination of lidocaine and remifentanil is more effective than either pretreatment alone in reducing pain on injection of propofol.

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.

Endothelial dysfunction after exposure to cobalt chloride enhanced vascular contractility.

Brief exposure to cobalt chloride augmented vascular contractility. We hypothesized that endothelial dysfunction plays a role in the augmentation of aortic contractility, after brief exposure to cobalt chloride. Rat aortic ring preparations were mounted in organ baths, exposed to cobalt chloride (0.3-300µmol/L) for 30min, and then subjected to contractile agents or relaxants 1 and 5h after the end of exposure. Presence of cobalt chloride did not affect the contractile response to phenylephrine. Brief exposure to cobalt chloride, however, even at 5h after the end of exposure, not only augmented contractile responses to KCl or phenylephrine but also attenuated the relaxant response to acetylcholine. The mechanical denudation of endothelium or inhibition of endothelial nitric oxide synthase with 100µmol/L N(ω)-nitro-l-arginine methyl ester abolished the augmentation of contractile responses. Pre-treatment with 150units/mL of superoxide dismutase also abrogated the augmented contractile responses. Brief exposure to cobalt chloride did not affect the contractile response to phorbol dibutyrate in the presence or absence of calcium, or the expression of HSP70. In conclusion, endothelial dysfunction plays an important role in the augmentation of aortic contractility, after brief exposure to cobalt chloride.

The effect of lavender oil on stress, bispectral index values, and needle insertion pain in volunteers.

OBJECTIVES: The purpose of this study was to investigate whether lavender oil aromatherapy can reduce the bispectral index (BIS) values and stress and decrease the pain of needle insertion in 30 volunteers. SUBJECTS AND METHODS: Thirty (30) healthy volunteers were randomly allocated to 2 groups: the experimental group received oxygen with a face mask coated with lavender oil for 5 minutes, and the control group received oxygen through a face mask with no lavender oil for 5 minutes. The stress level (0=no stress, 10=maximum stress), BIS value, and pain intensity of needle insertion (0=no pain, 10=worst pain imaginable) were measured. RESULTS: There were no significant differences in age, sex, height, and weight between the two groups. Stress level, BIS value, and pain intensity of needle insertion before aromatherapy were similar between the two groups. However, the stress values (p<0.001) and BIS value (p<0.001) after aromatherapy were significantly reduced compared with the control. In addition, the pain intensity of needle insertion was significantly decreased after aromatherapy compared with the control (p<0.001). CONCLUSIONS: Lavender aromatherapy in volunteers provided a significant decrease in the stress levels and in the BIS values. In addition, it significantly reduced the pain intensity of needle insertion.

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.

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.

Antiemetic efficacy of dexamethasone combined with midazolam after middle ear surgery.

OBJECTIVES: To evaluate the antiemetic efficacy of dexamethasone combined with midazolam after middle ear surgery. STUDY DESIGN: A prospective, randomized, double-blind, placebo-controlled study. SETTING: University hospital. SUBJECTS AND METHODS: The study population consisted of 120 American Society of Anesthesiologists physical status I or II, adult female patients undergoing middle ear surgery under general anesthesia. Patients were randomized into three groups of 40 each who received a dexamethasone dose of 10 mg/kg (group D), a combination of dexamethasone 10 mg and midazolam 0.075 mg/kg (group DM), and normal saline (group C) immediately after the induction of anesthesia. The incidence of nausea and vomiting, usage of rescue antiemetics, pain intensity, and side effects, such as headache and dizziness, were assessed during the first 24 hours after surgery. RESULTS: The overall incidence of nausea and vomiting was significantly lower in group D (35%, P < 0.05) and group DM (25%, P < 0.05) compared with that in group C (65%). The incidences of vomiting and usage of rescue antiemetic drugs in group DM were lower than those in group D (P < 0.05). There were no significant differences among groups in pain intensity and side effects, such as headache and dizziness. CONCLUSIONS: The combination of dexamethasone and midazolam was better than dexamethasone alone in reducing the incidence of vomiting and the rescue antiemetic requirements in women patients undergoing middle ear surgery. However, this combination treatment did not significantly decrease the overall incidence of nausea and vomiting compared with the use of dexamethasone alone.

Heat shock-induced augmentation of vascular contractility is independent of rho-kinase.

In a previous study, we demonstrated that heat shock augments the contractility of vascular smooth muscle through the stress response. 2. In the present study, we investigated whether Rho-kinases play a role in heat shock-induced augmentation of vascular contractility in rat isolated aorta. 3. Rat aortic strips were mounted in organ baths, exposed to 42 C for 45 min and subjected to contractile or relaxant agents 5 h later. 4. The level of expression of Rho-kinases in heat shock-exposed tissues was no different to that of control tissues, whereas heat shock induced heat shock protein (Hsp) 72 at 3 and 5 h. Heat shock resulted in an increase in vascular contractility in response to phenylephrine 5 h later. 5. The Rho-kinase inhibitors Y27632 (30 nmol/L-10 mmol/L) or HA 1077 (10 nmol/L-10 mmol/L) relaxed 1.0 mmol/L phenylephrine-precontracted vascular strips in a concentration-dependent manner; these effects were attenuated in heat shock-exposed strips. Pretreatment with Y27632 resulted in greater inhibition of the maximum contraction in control strips compared with those in heat shock-exposed strips. 6. The results of the present study suggest that Rho-kinases are unlikely to be involved in heat shock-induced augmentation of vascular contractility.

Role of PKC, tyrosine kinases, and Rho kinase in alpha-adrenoreceptor-mediated PASM contraction.

Our objectives were to identify the relative contributions of intracellular free Ca2+ concentration ([Ca2+]i) and myofilament Ca2+ sensitivity in the pulmonary artery smooth muscle (PASM) contractile response to the alpha-adrenoreceptor agonist phenylephrine (PE) and to assess the role of PKC, tyrosine kinases (TK), and Rho kinase (ROK) in that response. Our hypothesis was that multiple signaling pathways are involved in the regulation of [Ca2+]i, myofilament Ca2+ sensitization, and vasomotor tone in response to alpha-adrenoreceptor stimulation of PASM. Simultaneous measurement of [Ca2+]i and isometric tension was performed in isolated canine pulmonary arterial strips loaded with fura 2-AM. PE-induced tension development was due to sarcolemmal Ca2+ influx, Ca2+ release from inositol 1,4,5-trisphosphate-dependent sarcoplasmic reticulum Ca2+ stores, and myofilament Ca2+ sensitization. Inhibition of either PKC or TK partially attenuated the sarcolemmal Ca2+ influx component and the myofilament Ca2+ sensitizing effect of PE. Combined inhibition of PKC and TK did not have an additive attenuating effect on PE-induced Ca2+ sensitization. ROK inhibition slightly decreased [Ca2+]i but completely inhibited myofilament Ca2+ sensitization. These results indicate that PKC and TK activation positively regulate sarcolemmal Ca2+ influx in response to alpha-adrenoreceptor stimulation in PASM but have relatively minor effects on myofilament Ca2+ sensitivity. ROK is the predominant pathway mediating PE-induced myofilament Ca2+ sensitization.