Inhibition of Neuromuscular Contractions of Human and Rat Colon by Bergamot Essential Oil and Linalool: Evidence to Support a Therapeutic Action.

Bergamot essential oil (BEO) added to food and drink promotes a citrus flavour. Folklore suggests benefits on gastrointestinal functions but with little supporting evidence. BEO and major constituents (linalool, limonene, linalyl acetate) were therefore examined for any ability to influence neuromuscular contractions of human and rat colon. Circular muscle strips (macroscopically-normal human colon obtained following ethical approval at cancer surgery; Sprague-Dawley rats) were suspended in baths (Krebs solution; 37 °C; 5% CO2 in O2) for measurement of neuronally-mediated contractions (prevented by tetrodotoxin or atropine) evoked by electrical field stimulation (5 Hz, 0.5 ms pulse width, 10s/minute, maximally-effective voltage), or contractions evoked by KCl (submaximally-effective concentrations). BEO and each constituent concentration dependently inhibited neuronally-mediated and KCl-induced contractions. In human: apparent pIC50 for BEO (volume/volume Krebs), respectively, 3.8 ± 0.3 and 4.4 ± 0.3; Imax 55.8% ± 4.2% and 37.5% ± 4.2%. For the constituents, the rank order of potency differed in human (linalool > limonene >> linalyl-acetate) and rat colon (linalyl-acetate > limonene = linalool), but rank order of efficacy was similar (linalool >> (BEO) = linalyl-acetate >> limonene). Thus, linalool had high efficacy but greater potency in human colon (Imax 76.8% ± 6.9%; pIC50 6.7 ± 0.2; n = 4) compared with rat colon (Imax 75.3% ± 1.9%; pIC50 5.8 ± 0.1; n = 4). The ability of BEO and linalool to inhibit human colon neuromuscular contractility provides a mechanism for use as complementary treatments of intestinal disorders.

Clinical value of immunohistochemically detected lymphovascular space invasion in early stage cervical carcinoma.

BACKGROUND: This study investigates the clinical significance of lymphovascular space invasion (LVSI) as detected by hematoxylin and eosin (LVSI-H&E) and immunohistochemistry (LVSI-IHC) in early stage cervical carcinoma. METHODS: Single representative sections from 97 patients with early stage squamous cell cervical cancer were immunostained with pancytokeratin and CD31 endothelial cell marker antibodies. The H&E sections and their corresponding immunostained sections were reexamined to identify LVSI. Associations between LVSI with clinicopathological factors were sought. RESULTS: Overall, LVSI was present in 29 (29.9%) and absent in 68 (70.1%) by IHC, as compared with 18 cases (18.6%) and 79 cases (81.4%), respectively, by H&E. Statistical analysis revealed a significant association between LVSI-H&E and nodal metastasis (P = .004). Follow-up data were available for 76 patients. The median follow-up period was 64 months. During follow-up, 7 of 24 patients with recurrent disease had evidence of LVSI-H&E as opposed to 3 of 52 cases with no recurrence. There was a significant association between tumor recurrence and LVSI-H&E (P = .009). The 5-year recurrence-free survival was 30% for the group with LVSI-H&E compared with 73% without. There was a significant difference in the recurrence-free survival between the two groups (P = .002). In contrast LVSI-IHC was found to be associated with no pathological factors, and survival analysis revealed no statistically significant association with recurrence or survival. CONCLUSION: LVSI-H&E in early stage cervical cancer remains an important predictive factor of recurrent disease and reduced disease-free interval. Immunohistochemically detected LVSI is a common event and seems to be of no clinical value.