R.N.V. Prasad

Aphrodisiac properties of Tribulus terrestris extract (Protodioscin) in normal and castrated rats.

Tribulus terrestris (TT) has long been used in the traditional Chinese and Indian systems of medicine for the treatment of various ailments and is popularly claimed to improve sexual functions in man. Sexual behaviour and intracavernous pressure (ICP) were studied in both normal and castrated rats to further understand the role of TT containing protodioscin (PTN) as an aphrodisiac. Adult Sprague-Dawley rats were divided into five groups of 8 each that included distilled water treated (normal and castrated), testosterone treated (normal and castrated, 10 mg/kg body weight, subcutaneously, bi-weekly) and TT treated (castrated, 5 mg/kg body weight, orally once daily). Decreases in body weight, prostate weight and ICP were observed among the castrated groups of rats compared to the intact group. There was an overall reduction in the sexual behaviour parameters in the castrated groups of rats as reflected by decrease in mount and intromission frequencies (MF and IF) and increase in mount, intromission, ejaculation latencies (ML, IL, EL) as well as post-ejaculatory interval (PEI). Compared to the castrated control, treatment of castrated rats (with either testosterone or TT extract) showed increase in prostate weight and ICP that were statistically significant. There was also a mild to moderate improvement of the sexual behaviour parameters as evidenced by increase in MF and IF; decrease in ML, IL and PEI. These results were statistically significant. It is concluded that TT extract appears to possess aphrodisiac activity probably due to androgen increasing property of TT (observed in our earlier study on primates).

Effects on hemostasis after two-year use of low dose combined oral contraceptives with gestodene or levonorgestrel.

We studied 67 healthy women who were randomly allocated to receive third generation gestodene (Gynera®) or second generation levonorgestrel (Microgynon 30®) combina tion of low-dose estrogen oral contraceptives (OCs) for their hemostatic effects over 2 years. Hemostatic changes were ap parent within 3 months of OC use. Hematocrit (Hct) was not affected, but hemoglobin (Hb) concentration decreased by 18 months. Shortened prothrombin time (PT) and activated plasma thromboplastin time (APTT) were associated with elevated fi brinogen within the 12-month use of both OCs. Factor VII was reduced only in Micro 30 during the 18 months of use. En hanced thrombin-antithrombin (TAT)-complex level was seen at 18 months of Gynera use. Prothrombin fragment 1+2 (F1+2) rise was seen at 3 months with Micro 30. Reduced antithrombin III (ATIII) activity was seen at 18 months with Gynera and at 24 months with Micro 30. Increased protein C activity was seen at 3 months and reduced protein S occurred at 18 months of Gynera use. Tissue plasminogen activator (t-PA) activity was enhanced for 6 months in both OCs with raised D-dimer levels for 12 months with Gynera and 6 months with Micro 30. De creased t-PA antigen was seen at 18 months and decreased urokinaselike plasminogen activator (u-PA) antigen occurred throughout the 24 months of both OCs use. Enhanced u-PA activity was only seen in Gynera users. Elevated plasminogen levels were apparent throughout both OCs use. PAI-1 levels were significantly decreased with Micro 30. With Gynera, the decreased PAI-1 activity was seen only at 18 months and PAI-1 antigen at 12 months. No change in platelets and von Wil lebrand factor (vWF) were seen in long-term OC use except that β-thromboglobulin (β-TG) showed decreased trends reaching statistical significance by 18 and 24 months of Micro 30 use and by 24 months of Gynera use. A further significant decrease in β-TG, u-PA antigen, ATIII, and protein S levels were seen 3 months after pill stoppage compared with pretreat ment levels. Activated protein C resistance (APCR) was nega tive in all subjects before and during OC use. The study indi cated dynamic balance between coagulation and fibrinolysis with no endothelial activation. However, because some hemo static markers showed wide fluctuations during OC use, a longer term study is warranted to investigate any adverse he mostatic changes that might enhance the risks of venous thromboembolism in Asian subjects known to be less prone to thrombosis. Key Words: Oral contraceptives—Hemostasis.

Hemostatic status and fibrinolytic response potential at different phases of the menstrual cycle

Coagulation and fibrinolytic variables including platelet function and endogenous fibrinolytic response were determined in 30 normal healthy women volunteers not on any known medication during the period of study. They were between 18 years and 38 years old and had normal menstrual cycles of between 28 days and 30 days. Blood samples were obtained within one menstrual cycle and after having fasted overnight within days 1 to 3 (menstruation), 5 to 9 (follicular), 10 to 14 (mid-cycle), and 21 to 26 (luteal) of the menstrual cycle. Analysis of variance (ANOVA) showed no significant differences in the hemostatic parameters studied between the phases of the menstrual cycle except for a reduced D-dimer level at mid-cycle. Significant fibrinolytic response was seen after venous occlusion but they were not significantly different between the phases of the menstrual cycle. The women were then divided into either normal weight (n=22) or overweight (n=8) according to World Health Organization (WHO) classification and the data reanalyzed. Elevated tissue plasminogen activator antigen and plasminogen activator inhibitor-1 levels except at menstruation and total protein S except at follicular phase were observed in overweight women together with increased plasminogen level only at luteal phase. Significant endogenous fibrinolytic response seen during the menstrual cycle was not different between normal and overweight women. The study demonstrated that systemic coagulation, fibrinolysis, and platelet function were probably not influenced by natural hormonal changes occurring during the menstrual cycle except for an associated reduced fibrinolytic state at mid-cycle. The hemostatic system in this small group of healthy overweight women studied appeared to be physiologically compromised.

Hemostatic and fibrinolytic status in patients with ovarian cancer and benign ovarian cysts: could D-dimer and antithrombin III levels be included as prognostic markers for survival outcome?

We determined the hemostatic and fibrinolytic status in 60 patients with ovarian cancer and benign ovarian cysts. Hypercoagulation, increased platelets, and enhanced fibrinolysis were seen in patients with preoperative ovarian cancer compared to patients with benign ovarian cysts. Enhanced thrombin generation, evidenced by increased F1+2 and decreased antithrombin III (ATIII) levels with further enhanced fibrinolysis by elevated D-dimer, was seen in advanced cancer. Ten ovarian cancer patients died within 13 months after diagnosis and another died at 24 months, all from advanced stage of cancer, except one from stage IC cancer who died at 11. months. The survival rates from the disease at 13 months and 24 months were 66.7% and 45%, respectively. Most of the patients had gone through the complete course of chemotherapy, and those patients still alive have been disease free between 13 and 42 months. No statistical relationships for the hemostatic parameters studied in ovarian cancer patients could be found between those who died and those still living 13 and 24 months after diagnosis, except for ATIII and D-dimer levels. Elevated D-dimer levels were associated with those who died within 13 and 24 months from the disease, and the decreased ATIII levels only reached statistical significance by 24 months. It could be suggested that these two parameters might be useful as systemic prognostic markers in survival outcome from the disease for the first 24 months in advanced ovarian cancer, in addition to the known correlation with the International Federation of Gynecology and Obstetrics stage. Key Words: Hemostatic—fibrinolytic—Ovarian cancer.

Preinduction cervical priming with PGE2 vaginal film in primigravidae — A randomised, double blind, placebo controlled study

Previous reports with an 850 micrograms prostaglandin E2 film for cervical ripening before induction of labour in term pregnancy have been favourable. These studies however had no controls. The present study compares this PGE2 vaginal film with a nonmedicated similar vaginal film (placebo) for preinduction cervical ripening in primigravid women at term. A total of 69 women with modified Bishops cervical scores 1-5 were assigned randomly to either the PGE2 group (33 women) or placebo group (36 women). Cervical score assessments were made at 12 and 24 hours after which labour was induced by amniotomy and oxytocin infusion. Although the cervical scores between placebo and PGE2 groups at 12 and 24 hours were not significantly different, the scores were marginally better with the prostaglandin film. Pregnancy outcome was satisfactory in both groups with no perinatal or maternal mortality and morbidity. The caesarean rate was 30.6% in the placebo group and 24.2% in the PGE2 group. This study emphasizes the need for a control group when studying the success of agents used for ripening the pregnant cervix at term.

Histaminergic effect of crude papaya latex on isolated guinea pig ileal strips

In the present study, we investigated the effect of the crude latex of Carica papaya L. (CPX) on isolated guinea pig ileal strips. CPX (0.5-512 microg/ml) caused concentration-dependent contraction of ileal strips suspended in Tyrode solution. The concentration of atropine (0.69 microM) that significantly blocked the contractile effect of acetylcholine on the isolated guinea pig ileum showed no significant effect on CPX- and histamine-induced contractions of the ileal strips. Mepyramine (87.6 nM) significantly blocked the contractile effect of histamine and CPX on the ileum. The same concentration of mepyramine, however, had no significant effect on acetylcholine-induced contraction of the isolated ileal strips. Removal of Ca2+ from the bathing medium abolished ileal contractions induced by acetylcholine, histamine and CPX. All the test substances were able to provoke ileal contractions after replacement of the Ca(2+)-free solution with Tyrode solution. Furthermore, 10(-5) M of nifedipine, a Ca(2+)-entry antagonist, reversibly inhibited the contractile effect of all the test substances on the ileal strips. Results of this study together appear to show that CPX-induced contraction of the isolated guinea pig ileum is mediated via H1-receptors and dependent on extracellular Ca2+ influx.

Oxytocic activity of thrombin: modulation of thrombin-induced gravid rat myometrial contractions by 5-hydroxytryptamine receptor antagonists.

Abstract Background: Thrombin possesses potent oxytocic activity in vitro and in vivo. This activity has been proposed to play a role in post-parturitional uterine contractions and possibly, preterm birth related to intrauterine hemorrhage. Previous workers have demonstrated that cyclo-oxygenase pathway may not play a significant role in oxytocic activity of thrombin. However, the role of 5-hydroxytryptamine (a mediator of some of the biological activities of thrombin) in the oxytocic activity of thrombin is unknown. The present study therefore aimed to examine the possible involvement of 5-hydroxytryptamine in thrombin-induced myometrial contractions. Methods: Effect of 5-hydroxytryptamine receptor antagonists on thrombin-induced contractions of isolated gravid rat myometrium was studied using isolated tissue bath system. Results: Thrombin-induced myometrial contractions were significantly and concentration-dependently inhibited by ketanserin and methysergide. Furthermore, 12±2% increase in the force of contractions of gravid rat myometrium pre-contracted with 5-hydroxytryptamine (1 μM) was provoked by 1 U/ml of thrombin. Thrombin-induced augmentation of the uterine stimulating effect of 5-hydroxytryptamine was characterized by pronounced increase in the contractile tone. Conclusions: 5-hydroxytryptamine may possibly play a role in oxytocic activity of thrombin. Uterine hyperactivity associated with intrauterine hemorrhage could hence involve thrombin-induced 5-hydroxytryptamine production in the uterus.