Chin Chen Chu

The cellular mechanisms of the antiemetic action of dexamethasone and related glucocorticoids against vomiting.

Glucocorticoids, used primarily as anti-allergic and anti-inflammatory drugs, are also effective, alone or combined with other antiemetics, for preventing nausea and vomiting. Dexamethasone, one of the glucocorticoids, has been suggested as a first-line drug for preventing low-level emetogenic chemotherapy- and radiotherapy-induced nausea and vomiting, and in patients with only one or two risks for postoperative nausea and vomiting (PONV). Dexamethasone combined with 5-HT3 or tachykinin NK1 antagonists is also suggested for higher-level emetogenic chemotherapy and radiotherapy and for patients at high risk for PONV. Glucocorticoids may act via the following mechanisms: (1) anti-inflammatory effect; (2) direct central action at the solitary tract nucleus, (3) interaction with the neurotransmitter serotonin, and receptor proteins tachykinin NK1 and NK2, alpha-adrenaline, etc.; (4) maintaining the normal physiological functions of organs and systems; (5) regulation of the hypothalamic-pituitary-adrenal axis; and (6) reducing pain and the concomitant use of opioids, which in turn reduces opioid-related nausea and vomiting.

Low-dose dexamethasone reduces nausea and vomiting after epidural morphine: a comparison of metoclopramide with saline

STUDY OBJECTIVE To compare the efficacy of a low dose of dexamethasone (5 mg) with metoclopramide 10 mg and saline in preventing nausea and vomiting after epidural morphine in posthysterectomy analgesia. DESIGN Randomized, placebo-controlled study. SETTING Inpatient surgery at Municipal Womens and Childrens General Hospital. PATIENTS 120 ASA physical status I and II women receiving epidural morphine for posthysterectomy analgesia. INTERVENTIONS All patients received epidural morphine 3 mg for postoperative analgesia. The dexamethasone group (n = 40) received dexamethasone 5 mg, the metoclopramide group (n = 40) received metoclopramide 10 mg, and the saline group (n = 40) received saline. MEASUREMENTS AND MAIN RESULTS The occurrence of nausea and vomiting appeared more frequently during 6 to 24 hours following the administration of epidural morphine. The total frequency of nausea and vomiting in the dexamethasone group was significantly lower than that of the metoclopramide and saline groups during this period, with reporting frequencies of 21%, 49%, and 53%, respectively (p <.05 each). However, the difference between metoclopramide and saline did not reach statistical significance. CONCLUSIONS Dexamethasone 5 mg was more effective than metoclopramide or saline in the prevention of nausea and vomiting associated with epidural morphine for postoperative analgesia.

Isobolographic analysis of interaction between nisoxetine‐ and mepivacaine‐induced spinal blockades in rats

Although nisoxetine has been shown to elicit cutaneous (peripheral) anesthesia, spinal (central) anesthesia with nisoxetine was not exposed. The aim of this study was to examine spinal anesthesia of nisoxetine and its influence on the antinociceptive action of mepivacaine. We compared nisoxetine with an established local anesthetic mepivacaine for spinal anesthesia after rats were intrathecally injected with drugs. The drugs were spinally administered alone as well as in combination, and their potencies were compared via dose–response curves and isobolographic analysis. We showed that nisoxetine, as well as mepivacaine elicited spinal anesthesia in dose‐dependent manners. On a 50% effective dose (ED50) basis, the spinal block effect of nisoxetine in motor function, proprioception, and nociception [0.99 (0.91–1.10), 0.85 (0.76–0.95), 0.82 (0.74–0.89)] was more potent (P < 0.05) than that of mepivacaine [1.28 (1.21–1.34), 1.14 (1.07–1.22), 0.99 (0.93–1.05)], respectively. Furthermore, the nociceptive/sensory blockade (ED50) was greater than the motor blockade in both nisoxetine and mepivacaine groups (P < 0.05). Saline group (vehicle) produced no spinal anesthesia. Coadministration of nisoxetine with mepivacaine displayed an additive effect. Our data reported nisoxetine produced significant anesthesia at spinal level, and additive interaction with the local anesthetic, mepivacaine. Intrathecal nisoxetine elicited more potent spinal anesthesia than mepivacaine.

Anticancer agent 2-methoxyestradiol improves survival in septic mice by reducing the production of cytokines and nitric oxide.

Cytokine production is critical in sepsis. 2-Methoxyestradiol (2ME2), an endogenous metabolite of estradiol, inhibits hypoxia-inducible factor 1&agr; (HIF-1&agr;) and is an antiangiogenic and antitumor agent. We investigated the effect of 2ME2 on cytokine production and survival in septic mice. Using i.p. LPS or cecal ligation and puncture (CLP), sepsis was induced in BALB/c mice that were simultaneously or later treated with 2ME2 or vehicle. Twelve hours after the LPS injection, serum and peritoneal fluid cytokine and nitric oxide (NO) levels were analyzed using enzyme-linked immunosorbent assay and the Griess reaction. Lung injuries were histologically analyzed, and liver and kidney injuries were biochemically analyzed. Survival was determined 7 days after LPS injection or CLP procedure. In vivo and in vitro effects of 2ME2 on LPS-induced macrophage inflammation were determined. The effect of 2ME2 on HIF-1&agr; expression, nuclear factor &kgr;B (NF-&kgr;B), and inducible NO synthase (iNOS) in LPS-treated RAW264.7 cells, a murine macrophage cell line, was determined using Western blotting. 2-Methoxyestradiol treatment reduced LPS-induced lung, liver, and kidney injury. Both early and late 2ME2 treatment prolonged survival in LPS- and CLP-induced sepsis. 2-Methoxyestradiol significantly reduced IL-1&bgr;, IL-6, TNF-&agr;, and NO levels in septic mice as well as in LPS-stimulated peritoneal macrophages. 2-Methoxyestradiol treatment also reduced the LPS-induced expression of HIF-1&agr;, iNOS, and pNF-&kgr;B in RAW264.7 cells, as well as iNOS and pNF-&kgr;B expression in siHIF-1&agr;-RAW264.7 cells. 2-Methoxyestradiol prolongs survival and reduces lung, liver, and kidney injury in septic mice by inhibiting iNOS/NO and cytokines through HIF-1&agr; and NF-&kgr;B signaling.

Nutrient deficiencies as a risk factor in Taiwanese patients with postherpetic neuralgia.

Postherpetic neuralgia (PHN) is the most common complication of herpes zoster (HZ). The aim of the present study was to compare the nutritional status of PHN patients with that of healthy controls, and then to identify risk factors for PHN using multivariate multiple logistic regressions. In the present cross-sectional study, we prospectively enrolled fifty PHN patients for at least 3 months and fifty healthy controls. We selected nine circulating nutrients including ionised Ca, Zn, retinol, folic acid, vitamin B12, vitamin C, α-tocopherol, γ-tocopherol and lycopene associated with both immunity and the modulation of neuropathic pain, and measured their concentrations in plasma/serum. Concentrations of ionised Ca, Zn, vitamin C and vitamin B12 were significantly lower in PHN patients than in controls after excluding those patients receiving supplements since the outbreak of HZ. The prevalence of either mild/marginal or severe deficiencies for any of the nine selected circulating nutrients in PHN patients (92 %) was much higher than that in controls (46 %) (P < 0·001). Lower concentrations of vitamin C ( ≤ 45·0 μmol/l), ionised Ca ( ≤ 1·05 mmol/l) and Zn ( ≤ 0·91 g/l) were found to increase independently the risk of PHN using binary variable (dichotomy) analyses with both PHN patients and controls in a multivariate logistic regression analysis. No significant correlations existed between the risks of PHN and the concentrations of retinol, folic acid, vitamin B12, lycopene or α:γ-tocopherol ratios. Thus, lower concentrations of circulating nutrients, namely vitamin C, ionised Ca or Zn, are probably a risk factor in Taiwanese patients with PHN.

Rimantadine and 2‐adamantanamine elicit local anesthesia to cutaneous nociceptive stimuli in a rat model

The aim of this study was to investigate infiltrative cutaneous anesthesia of 2‐adamantanamine and rimantadine. After subcutaneous injections of drugs in rats, the blockade of cutaneous trunci muscle reflex by 2‐adamantanamine and rimantadine was evaluated. Lidocaine, a common local anesthetic, was used as control. We showed that rimantadine and 2‐adamantanamine as well as the local anesthetic lidocaine produced infiltrative anesthesia of skin in a dose‐dependent fashion. Saline (vehicle) group displayed no cutaneous anesthesia. The relative potency of these drugs was rimantadine [23.8 (21.1–26.8)] = lidocaine [26.4 (22.7–30.6)] > 2‐adamantanamine [64.6 (55.0–75.9)] (P < 0.01). On an equianesthetic basis [25% effective dose (ED25), ED50, and ED75], rimantadine and 2‐adamantanamine had longer duration of action than lidocaine (P < 0.05). Neither local injection of saline nor intraperitoneal administration of a large dose of drugs elicited cutaneous anesthesia (data not shown). These data demonstrated for the first time that rimantadine had a similar potent and longer duration of skin infiltrative anesthesia than did lidocaine, whereas 2‐adamantanamine had a less potency but longer duration of cutaneous anesthesia than did lidocaine.

Promazine and chlorpromazine for prolonged spinal anesthesia in rats

Though promazine and chlorpromazine elicited cutaneous anesthesia, no study of spinal anesthesia with chlorpromazine and promazine has been reported. This study was to examine whether chlorpromazine and promazine produce spinal anesthesia. Using a rat model via intrathecal injection, we tested spinal blockades of motor function and nociception by promazine, chlorpromazine or bupivacaine, and so were dose-response studies and durations. We demonstrated that chlorpromazine and promazine elicited dose-dependent spinal blockades in motor function and nociception. On the 50% effective dose (ED(50)) basis, the rank of potency of these drugs was bupivacaine>promazine>chlorpromazine (P<0.05 for the differences). On an equipotent basis (25% effective dose [ED(25)], ED(50), and ED(75)), the block duration caused by chlorpromazine or promazine was longer than that caused by the long-lasting local anesthetic bupivacaine (P<0.01 for the differences). Chlorpromazine and promazine, as well as bupivacaine, showed longer duration of sensory block than that of motor block. Our data reported that intrathecal promazine and chlorpromazine with a more sensory-selective action over motor blockade had less potent and longer-lasting spinal blockades when compared with bupivacaine.

Application of transesophageal echocardiography in removal of right atrial tumor thrombus of adrenal cortical carcinoma - A case report

Surgical removal of adrenal cortical carcinoma complicated by intra-atrial tumor thrombus is very difficult and risky if the removal of thrombus is incomplete, leading possibly to pulmonary embolism. Application of multiplane transesophageal echocardiography during surgical operation may help notifying the size and location of tumor thrombus and also help determining the completeness of the thrombus removal. We present a case of successful removal of adrenal cortical carcinoma with tumor thrombus extension to the right atrium under comprehensive anesthetic care including continuous intraoperative transesophageal echocardiography monitoring.