METHODS: Plasma SPM were measured in samples obtained from two double-blind controlled interventions. The first, included 51 women mean age 53 ± 1.5 years, undergoing breast surgery allocated to either intravenous saline, or dexamethasone (4 mg or 8 mg) after induction of anaesthesia. The second study included 31 women of mean age 44 ± 0.5 years undergoing laparoscopic gynecological surgery that were allocated to either saline, or dexamethasone (4 mg). SPM (18-HEPE, 17-HDHA, RvE2, RvD1 17R-RvD1 and RvD2) were measured in plasma collected prior to induction of anaesthesia and at 24 h, and 6 weeks post-surgery. Pain was assessed using a verbal analogue scale at discharge from the post-anaesthesia recovery unit. The data from each study was combined to examine the effect of dexamethasone on plasma SPM. The relationship between pain score and SPM was examined using ordinal logistic regression.
RESULTS: The SPM 18-HEPE, 17-HDHA, RvE2, RvD1 17R-RvD1 and RvD2 were detectable in all plasma samples. There was no significant difference in any SPM due to dexamethasone over the duration of the study. There was a fall in 17-HDHA between baseline and 24 h in both the dexamethasone and saline groups (P = 0.003) but no change in the downstream SPM (RvD1, 17R-RvD1 and RvD2) or 18-HEPE and RvE2. Pain score was negatively related to levels of RvE2 measured prior to induction of anaesthesia (rho = -0.2991, P = 0.006) and positively related to BMI (rho = 0.279, P = 0.011). In ordinal logistic regression the odds ratio for RvE2 was 0.931 (CI 0.880, 0.986; P = 0.014); after adjusting for the effect of BMI indicating that an increase in RvE2 of 1 pg/ml would result in a 6.9 % fall in pain score. Allocation to a dexamethasone group did not influence the pain score or the relationship between RvE2 and pain score.
CONCLUSION: Dexamethasone administered as an anti-emetic does not affect plasma SPM levels. An elevated RvE2 level prior to surgery is predictive of a lower perceived pain score post-anaesthesia.
METHODS: In three double-blind phase 3 studies, patients receiving HEC or MEC were randomized 1:1 to receive oral rolapitant 180 mg or placebo prior to chemotherapy plus 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone therapy. Patients completed the FLIE questionnaire on day 6 of cycle 1. Endpoints included FLIE total score, nausea and vomiting domain scores, and the proportion of patients with no impact on daily life (total score >108 [range 18-126]). We performed a prespecified analysis of the MEC/anthracycline-cyclophosphamide (AC) study and a post hoc analysis of two pooled cisplatin-based HEC studies.
RESULTS: In the pooled HEC studies, rolapitant significantly improved the FLIE total score (114.5 vs 109.3, p
RECENT FINDINGS: The cause of hyperemesis is continuing to be elaborated. Recent data attest to the effectiveness of the oral doxylamine-pyridoxine in NVP. Follow-up data of children exposed in early pregnancy to doxylamine-pyridoxine for NVP are reassuring. Evidence is increasing for ginger as an effective herbal remedy for NVP. Metoclopramide is effective in NVP and hyperemesis gravidarum, with a good balance of efficacy and tolerability. A recent large-scale study on first trimester exposure to metoclopramide is reassuring of its safety. Evidence is emerging for the treatment of acid reflux to ameliorate NVP. The role of corticosteroids for hyperemesis gravidarum remains controversial. Transpyloric feeding may be warranted for persistent weight loss, despite optimal antiemetic therapy.
SUMMARY: Women with significant NVP should be identified so that they can be safely and effectively treated.
METHODS: A crude methanol extract of the aerial parts of Isodon rugosus (Ir.Cr.) was used for both in vitro and in vivo experiments. The plant extract was tested on isolated rabbit jejunum preparations for possible presence of spasmolytic activity. Moreover, isolated rabbit tracheal and aorta preparations were used to ascertain the relaxant effects of the extract. Acetylcholinesterase and butyrylcholinesterase inhibitory activities of Ir.Cr were also determined as well as its antioxidant activity. The in vivo antiemetic activity of the extract was evaluated by using the chick emesis model, while the analgesic and antipyretic activities were conducted on albino mice.
RESULTS: The application of the crude extract of I. rugosus to isolated rabbit jejunum preparations exhibited relaxant effect (0.01-0.3 mg/ml). The Ir.Cr also relaxed K+(80 m M)-induced spastic contractions in isolated rabbit jejunum preparations and shifted the Ca+2 concentration response curves towards right (0.01-0.3 mg/ml). Similarly, the extract, when applied to the isolated rabbit tracheal preparations relaxed the carbachol (1 μM)--as well as K+ (80 mM)-induced contractions in a concentration range of 0.01-1.0 mg/ml. Moreover, it also relaxed (0.01-3.0 mg/ml) the phenylephrine (1 μM)- and K+ (80 mM)-induced contractions in isolated rabbit aorta preparations. The Ir.Cr (80 mg/kg) demonstrated antipyretic activity on pyrogen-induced pyrexia in rabbits as compared to aspirin as standard drug. The Ir.Cr also exhibited anti-oxidant as well as inhibitory effect on acetyl- and butyryl-cholinesterase and lipoxygenase (0.5 mg/ml).
CONCLUSIONS: The observed relaxant effect on isolated rabbit jejunum, trachea and aorta preparations caused by Ir.Cr is possibly to be mediated through Ca+2 channel blockade and therefore may provided scientific basis to validate the folkloric uses of the plant in the management of gastrointestinal, respiratory and cardiovascular ailments. The observed antioxidant activity as well as the lipoxygenase inhibitory activity may validate its traditional use in pain and inflammations.