Cocaine downregulates beta-adrenergic receptors in pregnant sheep myometrium.

Cocaine abuse is associated with premature labor. Although cocaine is known to competitively inhibit beta-adrenergic receptor binding, cocaine's effect on receptor downregulation is uncertain. This study was designed to determine the in vitro effect of cocaine on downregulation of beta-adrenergic receptors in pregnant myometrium. Pregnant sheep myometrium was incubated with either cocaine, isoproterenol, or a cocaine metabolite, benzoylecgonine. Membrane fractions were assayed for beta-adrenergic receptors using (125I)-cyanopindolol and the beta 2-adrenergic antagonist ICI 118,551. We found that cocaine (10(-6) to 10(-4) mol/L), but not benzoylecgonine, downregulated both beta 1- and beta 2-adrenergic receptors, but did not further augment receptor downregulation by isoproterenol. The 46% decrease in beta-adrenergic receptors seen after exposure to cocaine was similar to the 53% decrease seen after isoproterenol. We hypothesize downregulation of beta-adrenergic receptors by cocaine may play a role in the association of cocaine abuse with premature labor.

Inhibition of adhesion reformation in the rabbit model by meclofenamate: an inhibitor of both prostaglandin and leukotriene production.

OBJECTIVE: To determine the relative ability of meclofenamate sodium, a water-soluble inhibitor of both prostaglandin and leukotriene synthesis, to inhibit adhesion reformation. DESIGN: Prospective, randomized study in a rabbit model. INTERVENTIONS: Laparotomies were performed on mature New Zealand White rabbits, and each uterine horn was devascularized and traumatized with unipolar electrocautery. One week later, adhesions were microsurgically lysed. Each rabbit was randomly assigned to one of five different groups, and different solutions or an adhesion barrier were placed into the peritoneal cavities before closure: [1] control, 40 mL of normal saline (n = 8); [2] meclofenamate, 1.75 mg/mL in 40 mL of normal saline (n = 7); [3] Hyskon, 40 mL of 32% dextran-70 (n = 6); [4] meclofenamate 1.75 mg/mL in 40 mL of 32% dextran-70 (n = 6); and [5] TC-7, 40 mL of normal saline plus oxidized regenerated cellulose fabric, Interceed, placed over the site of adhesion lysis (n = 6). Two weeks later, adhesion reformation was scored according to percent involvement of each uterine horn (0 to 4), and adhesion density (0 to 1) and compared using a one-factor analysis of variance. RESULTS: Adhesion reformation was greatest in the control group (mean score +/- SEM, 3.7 +/- 0.4) and was decreased, but not significantly, in the Hyskon group (2.7 +/- 0.4). Compared with the control group, reformation was significantly decreased in the meclofenamate group (2.3 +/- 0.2), the TC-7 group (2.0 +/- 0.5), and the meclofenamate/Hyskon group (1.1 +/- 0.3). This last group was also decreased compared with the meclofenamate and Hyskon groups. CONCLUSION: Meclofenamate significantly inhibits adhesion reformation in the rabbit model, especially when used in combination with a 32% dextran-70 solution.

Cocaine selectively inhibits beta-adrenergic receptor binding in pregnant human myometrium.

OBJECTIVE: This study evaluated the in vitro effects of cocaine on the binding characteristics of alpha- and beta-adrenergic receptors from pregnant human myometrium. STUDY DESIGN: By means of membrane fractions from myometrium obtained from 26 women at term undergoing cesarean section, equilibrium binding assays were performed with tritiated dihydroergocryptine for alpha-adrenergic receptors and iodine 125-cyanopindolol for beta-adrenergic receptors. Equilibrium competition curves were determined with and without cocaine. Results were compared by one-way analysis of variance. RESULTS: Cocaine inhibited beta-adrenergic receptor binding (inhibition constant = 132 mumol/L) but had little effect on alpha-adrenergic receptor binding (inhibition constant = 1.63 mmol/L). Benzoylecgonine, a stable metabolite of cocaine, had no effect on binding to either receptor. CONCLUSION: Cocaine selectively inhibits myometrial beta-adrenergic receptor binding. This may alter the contractile equilibrium of the pregnant uterus and could explain, in part, the association of cocaine abuse with premature delivery.

The effect of cocaine on sperm motility characteristics and bovine cervical mucus penetration.

OBJECTIVES: To determine the in vitro effects of cocaine on sperm motility and bovine mucus penetration because cocaine abuse is associated with decreased sperm motility, and related compounds, such as procaine, are known to decrease sperm motility. DESIGN: Human semen samples were exposed to a range of cocaine concentrations and the effects quantified using computer-assisted sperm analysis and the bovine mucus penetration test. SETTING: University research laboratory. PATIENTS, PARTICIPANTS: Samples were obtained from 18 healthy volunteers. INTERVENTIONS: Normal semen samples were exposed to concentrations of cocaine ranging from 10(-11) to 10(-4) M. Motility characteristics were evaluated after 2 hours, and bovine mucus penetration was evaluated after 30 minutes, 1 hour, and 2 hours. Mucus penetration by washed sperm was also evaluated. MAIN OUTCOME MEASURES: Motility characteristics were evaluated using computer-assisted sperm analysis, and functional sperm motility was evaluated using the bovine mucus penetration test. RESULTS: Cocaine exposure decreased the percentage of motile sperm in a concentration-dependent manner with a maximum decrease of 23% at 10(-4) M but had no effect on other motility characteristics. Cocaine decreased bovine mucus penetration by 12% at high cocaine concentrations (10(-4) M), but increased penetration by 69% at low concentrations (10(-9) M). Washing sperm before cocaine exposure attenuated the increased sperm penetration. CONCLUSION: The ability of cocaine to decrease the percentage of motile sperm at high concentrations may explain the decreased sperm motility associated with cocaine use. Cocaine's ability to augment sperm penetration at low concentrations suggests an interaction of cocaine with the sperm adrenergic system.

Cocaine blocks extraneuronal uptake of norepinephrine by the pregnant human uterus.

Premature labor is one of the most common complications associated with cocaine abuse during pregnancy. Still, the effect of cocaine on the pregnant uterus is largely unknown. Although inhibition of neuronal uptake is the most important effect of cocaine in most tissues, after mid-pregnancy, the uterus has few functioning adrenergic nerve endings. To determine whether cocaine has any effect on uptake during pregnancy, we evaluated the ability of the term pregnant human uterus to take up [3H]-norepinephrine (9 x 10(-8) mol/L) and the ability of cocaine (10(-6)-10(-8) mol/L) to block this uptake. Because d-propranolol has been shown to block the direct effects of cocaine on the pregnant rabbit uterus, we also evaluated the ability of d-propranolol (2 x 10(-6) mol/L) to block the effect of cocaine on catecholamine uptake. The ability of the Uptake 2 inhibitor hydrocortisone (2 x 10(-5) mol/L) to block catecholamine uptake was also studied. We found that [3H]-norepinephrine was taken up by both the pregnant myometrium and endometrium, and that cocaine blocked this uptake by up to 55% at concentrations as low as 10(-7) mol/L. D-propranolol had no effect on the ability of cocaine to block catecholamine uptake. Hydrocortisone blocked uptake by the endometrium by 15% but did not block uptake by the myometrium. We conclude that the pregnant human uterus at term retains the ability to take up catecholamines and that cocaine blocks this extraneuronal uptake. This may explain, in part, the association of cocaine use with premature labor.

Abdominal wall characterization with magnetic resonance imaging and computed tomography. The effect of obesity on the laparoscopic approach.

Laparoscopic complications are most often related to insertion of the Veress cannula or primary trocar. We evaluated the midline abdominal walls of 33 women using magnetic resonance imaging (MRI) or computed tomography to determine if the location and angle of placement of the Veress cannula and primary trocar should be chosen according to the patient's weight to minimize the risk of both preperitoneal placement and retroperitoneal vessel injury. The anterior abdominal wall thickness was measured for three standard approaches used for placement of laparoscopic instruments through the umbilicus at both 45 degrees and 90 degrees from the horizontal. In addition, the distance from the base of the umbilicus to the retroperitoneal vessels was measured. We found that in the nonobese patient, both the Veress cannula and primary trocar can be inserted at 45 degrees, at either the lower margin or base of the umbilicus, with little risk of preperitoneal placement or major vessel injury. In the overweight patient the cannula and trocar can still be inserted at 45 degrees, but placement through the base of the umbilicus rather than the lower margin will minimize the chance of preperitoneal placement. In the majority of obese patients it is only by placing both the Veress cannula and sharp trocar through the base of the umbilicus at or near 90 degrees that preperitoneal placement can be avoided. Alternatively, an open laparoscopic technique can be considered in such high-risk patients to decrease the risk of major vessel injury.