ABSTRACT
Direct nitration of estradiol was carried out using metal nitrates on solid surfaces under mild condition, and a combination of bismuth nitrate pentahydrate impregnated KSF clay was found to be the best reagent to synthesize 2- and 4-nitroestradiol effectively. Furthermore, various basic side chains were introduced, through O-linker at C-3, to these nitroestradiols. The ability of these derivatives to cause cytotoxicity in Estrogen Receptor (ER)-positive and ER-negative breast cancer cell lines, as well as cancer cell lines of other origins, was examined. Qualitative structure activity relationship (SAR) has also been studied. We found that a basic side chain containing either a piperidine or morpholine ring, when conjugated to 2-nitroestradiol, was particularly effective at causing cytotoxicity in each of the cancer cell lines examined. Surprisingly, this effective cytotoxicity was even seen in ER-negative breast cancer cells.
Subject(s)
Antineoplastic Agents/pharmacology , Bismuth/chemistry , Estradiol/pharmacology , Nitrates/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Estradiol/chemical synthesis , Estradiol/chemistry , HeLa Cells , Hep G2 Cells , Humans , MCF-7 Cells , Molecular Structure , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
Arsenic (As) is a prevalent environmental toxin readily accessible for human consumption and has been identified as an endocrine disruptor. However, it is not known what impact As has on female sexual maturation. Therefore, in the present study, we investigated the effects of prepubertal exposure on mammary gland development and pubertal onset in female rats. Results showed that prepubertal exposure to 10 mg/kg of arsenite (As(III)) delayed vaginal opening (VO) and prepubertal mammary gland maturation. We determined that As accumulates in the liver, disrupts hepatocyte function and suppresses serum levels of the puberty related hormone insulin-like growth factor 1 (IGF-1) in prepubertal animals. Overall, this is the first study to show that prepubertal exposure to As(III) acts peripherally to suppress circulating levels of IGF-1 resulting in delayed sexual maturation. Furthermore, this study identifies a critical window of increased susceptibility to As(III) that may have a lasting impact on female reproductive function.
Subject(s)
Arsenites/toxicity , Environmental Pollutants/toxicity , Insulin-Like Growth Factor I/antagonists & inhibitors , Sexual Maturation/drug effects , Animals , Estradiol/blood , Female , Growth Hormone/blood , Humans , Insulin-Like Growth Factor I/metabolism , Liver/drug effects , Liver/pathology , Luteinizing Hormone/blood , Mammary Glands, Animal/drug effects , Mammary Glands, Animal/growth & development , Maternal-Fetal Exchange , Pregnancy , Rats, Sprague-Dawley , Sexual Maturation/physiologyABSTRACT
Peripartum cardiomyopathy (PPCM) is a rare form of heart failure of unknown etiology that is associated with late pregnancy and the early postpartum period. Although the complete pathogenesis of PPCM is not completely understood, the signs and symptoms are identical to those of left ventricular heart failure. The diagnosis of PPCM is made in a parturient only after other causes of heart failure are ruled out. Management of PPCM is similar to that of congestive heart failure with a few exceptions, such as avoiding the use of angiotensin-converting enzyme inhibitors during pregnancy. This report describes the presentation and anesthetic management of a parturient who was admitted with a diagnosis of severe preeclampsia in whom pulmonary edema and heart failure developed, necessitating emergency cesarean delivery under general anesthesia. The patient was subsequently given a diagnosis of PPCM.
Subject(s)
Cardiomyopathies/complications , Cesarean Section , Nurse Anesthetists , Pre-Eclampsia , Pulmonary Edema/complications , Adult , Critical Care , Female , Humans , Pregnancy , Severity of Illness IndexABSTRACT
Research indicates that using a combination of ketorolac and lidocaine in the administration of a Bier block results in significant postoperative analgesia and decreased inflammation; however, the optimal dose of ketorolac to coadminister with the local anesthetic has not been established. This study was performed to determine if a 20-mg dose of ketorolac is effective in providing prolonged postoperative analgesia without adverse effects. A total of 55 patients (29 lidocaine-ketorolac, 26 lidocaine-placebo) were enrolled in this randomized, double-blind, placebo controlled study. Pain was measured using a 0 to 10 visual analogue scale and analysis of postoperative analgesic requirements. Incidence of bruising and postoperative analgesic satisfaction scores were determined 48 hours following discharge. No difference in demographic variables, adverse effect profiles, or satisfaction scores was noted between groups. Visual analogue scale scores were increased in the placebo group in the hospital but not following discharge to home. There was also a prolonged time to postoperative analgesic requests in the ketorolac group compared with the placebo group following discharge to home, achieving statistical significance for the time to second analgesic request (P = .012). Based on the results of this study we recommend that 20 mg ketorolac be considered in intravenous regional anesthesia.
