Venous thromboembolisms and rheology in ovarian cancer patients after postoperative adjuvant paclitaxel and carboplatin therapy.

In ovarian cancer patients, chemotherapy can be an independent risk factor for the development of thromboembolic complications, such as venous thromboembolism (VTE). The factors and their values that lead to the development of VTE are remaining unknown in patients undergoing chemotherapy with paclitaxel and carboplatin. This study investigated serial rheological parameters (D-dimer, red blood cell count, hematocrit, and plasma viscosity) for VTE that developed following chemotherapy for ovarian cancer. Forty-eight ovarian cancer patients undergoing chemotherapy were enrolled in this study. A significant difference in the mean values of plasma viscosity and hematocrit was observed between the VTE group (n = 5) and the non-VTE group (n = 43) (P < 0.10). Univariate and multiple regression analyses by stepwise selection identified plasma viscosity as the independent variable associated with VTE development. The VTE incidence was the same as in previous reports. The results support the contention that plasma viscosity could be an index for development of VTE in ovarian cancer after chemotherapy.

Effect of pilocarpine on substance P and calcitonin gene-related peptide releases correlate with salivary secretion in human saliva and plasma.

WHAT IS KNOWN AND OBJECTIVE: Pilocarpine, a muscarinic receptor agonist, has been used for the treatment of dry mouth. Salivary glands are supplied with nerve fibres that contain neuropeptides, such as substance P, calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP), which are important modulators of salivation. It is known that measurement of salivary and plasma levels of neuropeptides is useful for assessing the dose-pharmacological effect relationship of drugs. The relationship between the action of pilocarpine and neuropeptides in humans has not been studied. Moreover, studies evaluate the usefulness of drug salivary levels in the pharmacological evaluation of drugs are scarce. The aim of this study was to examine the effects of pilocarpine on the levels of substance P-, CGRP- and VIP-like immunoreactive substances (IS) in saliva and plasma taken in healthy humans. METHODS: Five healthy male subjects participated in this study. Pilocarpine tablet (10 mg) or placebo tablet was orally administered with 100 mL of water. Each subject was administered placebo and drug with an interval of 4 weeks in between. Saliva was sampled before and at 20, 40, 60, 90, 120, 180 and 240 min after administration of the test substances. Venous blood samples (10 mL) were also taken from a forearm vein at each time interval. The samples were then enzyme immunoassayed using a highly sensitive system for substance P-, CGRP- and VIP-IS. The amount of saliva was measured by the Saxon test. RESULTS: A single oral administration of pilocarpine increased the release of salivary substance P-IS (the area under the concentration-time curve: AUC(0→240 min)) compared with the placebo. Pilocarpine also significantly increased the release of salivary CGRP-IS (AUC(0→240 min)). Pilocarpine significantly increased the release of plasma CGRP-IS. The salivary volume correlated with the salivary level of substance P and CGRP-IS (r = 0·84, P < 0·05 and r = 0·59, P < 0·05, respectively). AUC(0→240 min) for substance P-IS in saliva correlated with that for plasma (r = 0·78, P < 0·05). WHAT IS NEW AND CONCLUSION: Pilocarpine increases the release of salivary substance P and CGRP-IS. This suggests that one mechanism by which pilocarpine improves dry mouth is by local stimulation of neuropeptidergic nerves. Moreover, saliva levels of substance P showed good correlation with the plasma levels. The substance P levels in saliva and plasma may be good indicators of the effects of drugs used in dry mouth/xerostomic patients.