RESUMO
Approximately fifty percent of premenopausal women who smoke cigarettes or on nicotine replacement therapy are also on hormonal contraceptives, especially oral estrogen-progestin. Oral estrogen-progestin therapy has been reported to promote insulin resistance (IR) which causes lipid influx into non-adipose tissue and impairs Na+/K+ -ATPase activity, especially in the heart and kidney. However, the effects of nicotine on excess lipid and altered Na+/K+ -ATPase activity associated with the use of estrogen-progestin therapy have not been fully elucidated. This study therefore aimed at investigating the effect of nicotine on cardiac and renal lipid influx and Na+/K+ -ATPase activity during estrogen-progestin therapy. Twenty-four female Wistar rats grouped into 4 (n = 6/group) received (p.o.) vehicle, nicotine (1.0 mg/kg) with or without estrogen-progestin steroids (1.0 µg ethinyl estradiol and 5.0 µg levonorgestrel) and estrogen-progestin only daily for 6 weeks. Data showed that estrogen-progestin treatment or nicotine exposure caused IR, hyperinsulinemia, increased cardiac and renal uric acid, malondialdehyde, triglyceride, glycogen synthase kinase-3, plasminogen activator inhibitor-1, reduced bilirubin and circulating estradiol. Estrogen-progestin treatment led to decreased cardiac Na+/K+-ATPase activity while nicotine did not alter Na+/K+-ATPase activity but increased plasma and tissue cotinine. Renal Na+/K+-ATPase activity was not altered by the treatments. However, all these alterations were reversed following combined administration of oral estrogen-progestin therapy and nicotine. The present study therefore demonstrates that oral estrogen-progestin therapy and nicotine exposure synergistically prevents IR-linked cardio-renotoxicity with corresponding improvement in cardiac and renal lipid accumulation, oxidative stress, inflammation and Na+/K+-ATPase activity.
Assuntos
Anticoncepcionais Orais Combinados/farmacologia , Estrogênios/farmacologia , Etinilestradiol/farmacologia , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Levanogestrel/farmacologia , Miocárdio/enzimologia , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Progestinas/farmacologia , Animais , Anticoncepcionais Orais Combinados/toxicidade , Citoproteção , Combinação de Medicamentos , Sinergismo Farmacológico , Estrogênios/toxicidade , Etinilestradiol/toxicidade , Feminino , Mediadores da Inflamação/metabolismo , Rim/enzimologia , Rim/patologia , Levanogestrel/toxicidade , Metabolismo dos Lipídeos/efeitos dos fármacos , Miocárdio/patologia , Nicotina/toxicidade , Agonistas Nicotínicos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Progestinas/toxicidade , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
CONTEXT: Cardiometabolic disorders are rapidly becoming major public health challenges. Valproic acid (VPA) is a widely prescribed anticonvulsant drug. OBJECTIVE: We hypothesized that treatment with VPA would improve the regulation of glucose and atherogenic dyslipidemia through reduction in circulating corticosterone. METHODS: Female Wistar rats recieved (p.o.) combined oral contraceptive (COC) containing 1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel and valproic acid (VPA; 20 mg) for 8 weeks. RESULTS: Treatment with COC led to elevated fasting blood glucose, insulin, corticosterone, triglycerides (TG), TG/HDL-cholesterol ratio, insulin resistance (IR) and impaired glucose tolerance. VPA significantly attenuated the alterations induced by COC treatment, but did not affect the corticosterone level. However, VPA treatment led to significant increases in plasma insulin, corticosterone, atherogenic lipids and impaired glucose tolerance in rats not treated with COC. CONCLUSION: The findings in this study suggest that VPA mitigates against the development of COC-induced insulin resistance and dyslipidemia independent of elevated circulating corticosterone.
Assuntos
Anticonvulsivantes/farmacologia , Anticoncepcionais Orais Combinados/toxicidade , Corticosterona/sangue , Dislipidemias/tratamento farmacológico , Intolerância à Glucose/tratamento farmacológico , Ácido Valproico/farmacologia , Animais , Dislipidemias/induzido quimicamente , Feminino , Intolerância à Glucose/induzido quimicamente , Teste de Tolerância a Glucose , Ratos , Ratos WistarRESUMO
Oral contraceptives (OC) and smoking-derived nicotine (N) are known to synergistically increase the risk and severity of cerebral ischemia in women. Although it has been known for some time that long-term use of OC and nicotine will have an increased risk of peripheral thrombus formation, little is known about how the combination of OC and nicotine increases severity of brain ischemia. Recent laboratory studies simulating the conditions of nicotine exposure produced by cigarette smoking and OC regimen of women in female rats confirms that the severity of ischemic hippocampal damage is far greater in female rats simultaneously exposed to OC than to nicotine alone. These studies also demonstrated that the concurrent exposure of OC and nicotine reduces endogenous 17ß-estradiol levels and inhibits estrogen signaling in the brain of female rats. The endogenous 17ß-estradiol plays a key role in cerebrovascular protection in women during their pre-menopausal life and loss of circulating estrogen at reproductive senescence increases both the incidence and severity of cerebrovascular diseases. Therefore, OC and nicotine induced severe post-ischemic damage might be a consequence of lack of estrogen signaling in the brain. In the present review we highlight possible mechanisms by which OC and nicotine inhibits estrogen signaling that could be responsible for severe ischemic damage in females.
Assuntos
Isquemia Encefálica/induzido quimicamente , Anticoncepcionais Orais Combinados/toxicidade , Estimulantes Ganglionares/toxicidade , Nicotina/toxicidade , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Sinergismo Farmacológico , Estradiol/metabolismo , Antagonistas de Estrogênios/farmacologia , Moduladores de Receptor Estrogênico/farmacologia , Estrogênios/metabolismo , Etinilestradiol/toxicidade , Feminino , Mitocôndrias/metabolismo , Norgestrel/toxicidade , Fosforilação/fisiologia , Ratos , Receptores de Estrogênio/fisiologia , Transdução de Sinais , Fumar/efeitos adversosRESUMO
BACKGROUND: Nomegestrol acetate (NOMAC), a synthetic progestogen derived from 19-nor-progesterone, recently completed clinical trials for use with 17beta-estradiol in a new monophasic combined oral contraceptive. In this review, published as well as previously unpublished preclinical studies that detail the effects of NOMAC on estrogenic, progestogenic, and androgenic systems, as well as mineralocorticoid, glucocorticoid, bone, and metabolic indices are described. METHODS: In vitro assays to determine NOMAC structure-activity relationships used tissue derived from rat uteri. Transactivation profiles were performed using Chinese hamster ovary (CHO) cells transfected with cDNAs encoding human steroid receptors. Estrogenic and anti-estrogenic activities were monitored in vivo in rats as well as in vitro in human breast cancer cells. Standard in vivo techniques were used in rats to determine progestational activity; antigonadotropic, androgenic, mineralocorticoid, and glucocorticoid activities; as well as effects on bone and other metabolic indices. Ovulation inhibition was monitored in rats and primates. NOMAC's effects on cardiovascular systems were determined in dogs and primates. RESULTS: NOMAC was without significant agonistic or antagonistic activity for estrogen receptor alpha or beta in vitro, and inhibited ovulation in rats and monkeys (2.5 mg/kg and 1 mg/kg, respectively). NOMAC lacked androgenic, antimineralocorticoid, glucocorticoid, and metabolic activity and exhibited moderate anti-androgenic activity in rats. NOMAC did not affect bone mineral density (BMD) in rats or hemodynamic and electrophysiologic parameters in dogs and primates. CONCLUSIONS: NOMAC is a selective progestogen structurally similar to progesterone that has modest anti-androgenic activity and does not affect lipid or carbohydrate metabolism, BMD, or many cardiovascular parameters in selected animal models.
Assuntos
Megestrol/farmacologia , Norpregnadienos/farmacologia , Congêneres da Progesterona/farmacologia , Androgênios/química , Androgênios/farmacologia , Androgênios/toxicidade , Animais , Densidade Óssea/efeitos dos fármacos , Células CHO , Metabolismo dos Carboidratos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Anticoncepcionais Orais Combinados/farmacologia , Anticoncepcionais Orais Combinados/toxicidade , Cricetinae , Cães , Avaliação Pré-Clínica de Medicamentos , Estrogênios/química , Estrogênios/farmacologia , Estrogênios/toxicidade , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Macaca fascicularis , Masculino , Megestrol/química , Megestrol/toxicidade , Norpregnadienos/química , Norpregnadienos/toxicidade , Ovulação/efeitos dos fármacos , Congêneres da Progesterona/química , Congêneres da Progesterona/toxicidade , Ratos , Células Tumorais Cultivadas , Útero/efeitos dos fármacosRESUMO
Oral contraceptives are highly efficient and easily administered drugs; however, it must not be forgotten that they are composed of chemical substances which can be classified as potential carcinogens. Testing of a substance for genotoxicity represents a reliable approach both to evaluate the genetic hazard and to obtain information on its possible tumorigenic (cancerogenic) properties. The present study was undertaken to evaluate through carefully planned and controlled investigations the in vitro cytogenetic effects of oral contraceptives (ethynilestradiol and norgestrel mixed in the proportion 1:5) using three different concentrations, with two different durations of treatment (48 and 72 h), on two types of human cells (lymphocytes and fibroblasts) and a series of short-term test procedures: sister chromatid exchange (SCE), micronucleus test (MN), and chromosome aberrations (CA). In addition, the FISH procedure and in vitro anaphase and metaphase preparation analyses were performed. In contrast to CA and SCE frequencies, the frequency of MN in treated blood lymphocytes showed higher values by comparison with the controls, although the difference was statistically significant only for the lowest concentration (P = 0. 016). When using pancentromeric alphoid probes, the FISH procedure gave positive signals in more than 85% of micronuclei, clearly indicating that MN may contain whole chromosomes rather than acentric fragments. Unlike the lymphocytes, the fibroblasts showed dose-dependent effects, although those treated with the highest hormone concentrations showed an increased number of highly damaged cells (cytoplasmatic vacuolization, nuclear fragmentation, etc.), a decreased number of anaphase cells, a large number of which were abnormal, and a reduction of mitotic index. In conclusion, our data confirm that hormones do not induce structural chromosome aberrations in lymphocytes and indicate that ethynilestradiol and norgestrel have an aneugenic effect on fibroblast and lymphocyte cultures; FISH analysis on micronuclei from lymphocyte cultures and anaphase preparations from fibroblast cultures support this hypothesis. Teratogenesis Carcinog. Mutagen. 20:147-159, 2000.
Assuntos
Aneuploidia , Anticoncepcionais Orais Combinados/toxicidade , Anticoncepcionais Orais Hormonais/toxicidade , Dano ao DNA , Etinilestradiol/toxicidade , Fibroblastos/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Norgestrel/toxicidade , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/ultraestrutura , Aberrações Cromossômicas , Anticoncepcionais Orais Combinados/farmacologia , Anticoncepcionais Orais Hormonais/farmacologia , Relação Dose-Resposta a Droga , Etinilestradiol/administração & dosagem , Etinilestradiol/farmacologia , Fibroblastos/ultraestrutura , Humanos , Hibridização in Situ Fluorescente , Linfócitos/ultraestrutura , Testes para Micronúcleos , Norgestrel/administração & dosagem , Norgestrel/farmacologia , Segurança , Troca de Cromátide Irmã/efeitos dos fármacosRESUMO
Sexually mature female Wistar rats were given 0.05 mg ethinylestradiol (EE) + 0.5 mg norethisterone acetate (NET), or 0.1 mg EE + 1.0 mg NET for 6 or 12 sexual cycles, i.e., for 30 or 60 days. Rat hepatocytes, renal proximal tubule cells, ovarian granulosa cells and endometrial gland cells showed ultrastructural changes that correlated with the dose and duration of EE/NET treatment. The most common ultrastructural features were as follows: reduced RER, mitochondrial damage, and an increased number of lysosomes. The study has shown that EE/NET combinations used in oral contraception produce ultrastructural lesions, which may impair protein biosynthesis and energy production processes, and may simultaneously enhance cellular catabolism.
Assuntos
Endométrio/efeitos dos fármacos , Endométrio/ultraestrutura , Etinilestradiol/administração & dosagem , Etinilestradiol/toxicidade , Rim/efeitos dos fármacos , Rim/ultraestrutura , Fígado/efeitos dos fármacos , Fígado/ultraestrutura , Noretindrona/análogos & derivados , Ovário/efeitos dos fármacos , Ovário/ultraestrutura , Animais , Anticoncepcionais Orais Combinados/administração & dosagem , Anticoncepcionais Orais Combinados/toxicidade , Endométrio/metabolismo , Metabolismo Energético/efeitos dos fármacos , Feminino , Rim/metabolismo , Fígado/metabolismo , Microscopia Eletrônica , Noretindrona/administração & dosagem , Noretindrona/toxicidade , Acetato de Noretindrona , Ovário/metabolismo , Biossíntese de Proteínas , Ratos , Ratos WistarRESUMO
DT-5061, a steroid oral contraceptive which contains norethisterone (NET) and ethinyl estradiol (EE) in a ratio of 100:7, was administered orally to rats for 14 days in order to investigate a possible origin of the increased serum alkaline phosphatase (ALP). Increased serum total ALP was noted in rats receiving DT-5061 at 5.35 mg/kg/day or EE at 0.35 mg/kg/day. Electrophoresis of serum ALP revealed that both liver and bone-type ALP isozymes were increased in the DT-5061 5.35 mg/kg and EE 0.35 mg/kg groups, and the ratio of increase in the liver-type was greater than that in the bone-type although the increase in concentration of the bone-type was greater as compared to the liver-type. ALP level in the liver was elevated together with an increase in liver weight, consistently with the increased serum liver-type isozyme. However, neither histological changes indicative of cholestasis nor increase in serum leucine aminopeptidase, bilirubin, GOT or GPT were seen. No changes were observed in bone ALP activity; hence inconsistent with the increased serum bone-type isozyme. From these results, it is considered that the increased serum ALP induced by this drug was due to the increased liver-type isozyme induced in the liver and to the increased bone-type isozyme, and among the ingredients of this oral contraceptive, EE was mainly involved in the increased serum ALP induced by this drug.
Assuntos
Fosfatase Alcalina/sangue , Anticoncepcionais Orais Combinados/toxicidade , Anticoncepcionais Orais Hormonais/toxicidade , Etinilestradiol/toxicidade , Noretindrona/toxicidade , Administração Oral , Animais , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/enzimologia , Anticoncepcionais Orais Combinados/administração & dosagem , Anticoncepcionais Orais Hormonais/administração & dosagem , Combinação de Medicamentos , Etinilestradiol/administração & dosagem , Feminino , Isoenzimas/sangue , Fígado/efeitos dos fármacos , Fígado/enzimologia , Noretindrona/administração & dosagem , Ratos , Ratos Sprague-DawleyRESUMO
DT-5061, a steroid oral contraceptive which contains norethisterone (NET) and ethinyl estradiol (EE) was administered orally to adrenalectomized rats for 3 days to investigate involvement of the adrenals in the increased serum alkaline phosphatase (ALP). In addition, corticosterone or aldosterone were administered to the adrenalectomized rats to examine their effects on serum ALP. Increases in serum total ALP, liver-type and bone-type ALP isozymes were observed in rats with intact adrenals following administration of DT-5061, but these responses were not noted in adrenalectomized rats. Increases in liver weight and ALP activity in the liver after administration of the drug were reduced but not abolished in the adrenalectomized rats. The adrenalectomized rats receiving corticosterone showed increases in serum total ALP, liver-type ALP isozyme and liver weight but did not exhibit any increase in bone-type ALP isozyme. On the other hand, aldosterone did not increase and even reduced serum ALP although ALP activity in the liver was increased in the adrenalectomized rats.
Assuntos
Adrenalectomia , Fosfatase Alcalina/sangue , Anticoncepcionais Orais Combinados/toxicidade , Anticoncepcionais Orais Hormonais/toxicidade , Etinilestradiol/toxicidade , Noretindrona/toxicidade , Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/fisiologia , Aldosterona/farmacologia , Animais , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/enzimologia , Anticoncepcionais Orais Combinados/administração & dosagem , Anticoncepcionais Orais Hormonais/administração & dosagem , Cortisona/farmacologia , Combinação de Medicamentos , Etinilestradiol/administração & dosagem , Feminino , Isoenzimas/sangue , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Noretindrona/administração & dosagem , Ratos , Ratos Sprague-DawleyRESUMO
The possibility that risk of a atherosclerosis complication increases with oral contraceptive use was examined by studying the effect of oral pill containing 0.067 mg menstranol and 0.667 mg ehtynodiol diacetate/kg body weight on the metabolism of lipids in female rats fed a hypercholesterolemic diet for three months. Experimental group clearly exhibited higher levels of triglycerides and cholesterol in plasma and tissues, increase in aorta observed to be two folds. Increased hepatic cholesterogenesis was noted with treatment of oral contraceptive as indicated by higher activity of HMG-CoA reductase. Activity of lipoprotein lipase of extrahepatic tissue was depressed in experimental group. Activity of plasma LCAT, an enzyme involved in the transport of cholesterol from tissues, was also lower with treatment of oral contraceptive. However, activity of malic enzyme and glucose-6-phosphate dehydrogenase enhanced considerably with administration of oral pill. The increase in plasma and aortic cholesterol levels, increase in LDL+VLDL cholesterol and considerable decrease in HDL cholesterol in animals treated with oral contraceptives and fed with atherogenic diet, indicates that prolonged administration of oral pill may predispose towards atherosclerosis.
Assuntos
Arteriosclerose/etiologia , Anticoncepcionais Orais Sintéticos/toxicidade , Dieta Aterogênica , Diacetato de Etinodiol/toxicidade , Mestranol/toxicidade , Animais , Anticoncepcionais Orais Combinados/toxicidade , Feminino , Metabolismo dos Lipídeos , RatosRESUMO
The intraperitoneal median lethal dose of Cyclofem [Cyclo-Provera, C-P; depot-medroxyprogesterone acetate (Depo-Provera, DMPA)+estradiol cypionate (EC)] in mice was greater than 2500 mg/kg. The subcutaneous median lethal dose in mice and rats was greater than 1000 mg/kg. The suspension containing 50 mg/ml DMPA and 10 mg/ml EC used in all toxicology studies was not irritating to rabbit muscle. Chronic parenteral toxicity studies of Cyclofem were conducted in mice, rats and monkeys for 18, 22 and 24 months, respectively. Monthly doses were 2.5, 7.5 and 25 mg/kg Cyclofem in all species, 25 mg/kg DMPA and 25 mg/kg EC. Cyclofem was nontoxic but produced hormonal effects in all species. Decreased survival noted in the rodent studies was likely due to excessive EC dose. Mammary gland adenocarcinomas and pituitary adenomas were increased in the chronic rat study. Literature indicates the tumors were likely the result of the excessive hormone dose and were specific to rodents. In monkeys, Cyclofem was nontoxic, hormonally active, and noncarcinogenic at all doses including 50 times the human dose.
Assuntos
Estradiol/análogos & derivados , Acetato de Medroxiprogesterona/administração & dosagem , Acetato de Medroxiprogesterona/toxicidade , Adenocarcinoma/induzido quimicamente , Animais , Anticoncepcionais Orais Combinados/administração & dosagem , Anticoncepcionais Orais Combinados/toxicidade , Preparações de Ação Retardada , Combinação de Medicamentos , Estradiol/administração & dosagem , Estradiol/toxicidade , Feminino , Injeções Intramusculares , Injeções Intraperitoneais , Injeções Subcutâneas , Macaca mulatta , Masculino , Neoplasias Mamárias Experimentais/induzido quimicamente , Camundongos , Camundongos Endogâmicos ICR , Neoplasias Hipofisárias/induzido quimicamente , Coelhos , RatosRESUMO
Anovlar 21, a combination drug containing the oestrogen ethinyloestradiol and the progestin norethisterone acetate, was studied for its in vivo genotoxic effect on the bone marrow cells of Swiss albino mice. The chromosomal aberration assay and the micronucleus test were employed for the study. 0.08, 0.4, 0.8, 1.6, 3.2, 4.8, 6.4 and 8.0 mg/kg/day of the drug was orally administered for 15 consecutive days to mice. Bone marrow preparations were made 24 h after the final feeding. The lowest dose, 0.08 mg/kg, represents the human therapeutic range. Marrow preparations of mice fed 0.8 mg/kg/day for 15 days were made at 6, 12, 24, 48 and 96 h, and 1, 2 and 3 weeks and a time-yield analysis was carried out. Statistically significant increases in chromosomal aberrations were observed in animal groups fed doses of greater than or equal to 0.4 mg/kg/day. In the time-response study, the maximum frequency of aberrations was noted at 24 h, thereafter decreasing gradually with increasing time. But the drug did not induce a significant increase in the number of micronuclei in bone marrow erythrocytes at any of the doses or time intervals studied.
Assuntos
Anticoncepcionais Orais Combinados/farmacologia , DNA/efeitos dos fármacos , Etinilestradiol/toxicidade , Noretindrona/toxicidade , Animais , Medula Óssea/efeitos dos fármacos , Anticoncepcionais Orais Combinados/toxicidade , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Feminino , Camundongos , Testes para Micronúcleos , Testes de Mutagenicidade , Fatores de TempoRESUMO
In the experiments on mature females of 50 rats, 10 rabbits, 8 dogs it was established that a new gestagenic drug acetomepregenol was not toxic both for pregnant and nonpregnant animals. The two-month administration of the drug in the therapeutic and maximal doses did not exert the irreversible effects on the reproductive function and did not influence the embryonal and postnatal development of the offspring. A single administration of acetomepregenol in the critical periods of pregnancy was found to exert the embryotoxic effect which did not manifest itself during daily administration of the drug from the 6th through the 16th days of pregnancy.
Assuntos
Anticoncepcionais Orais Combinados/farmacologia , Pregnadienodiois/farmacologia , Animais , Anticoncepcionais Orais Combinados/toxicidade , Cães , Relação Dose-Resposta a Droga , Embrião de Mamíferos/efeitos dos fármacos , Feminino , Pregnadienodiois/toxicidade , Gravidez , Coelhos , Ratos , Reprodução/efeitos dos fármacos , Teratogênicos , Fatores de TempoRESUMO
The globulines anormalment precipitables (GAP), which have been reported to be raised in current and former oral contraceptive users, were measured in Nigerian subjects which included male volunteers. The results showed that GAP were present in males who had never used contraceptives and that the mean values were lowest in intrauterine contraceptive device (IUD) users and highest in females who had never used any contraceptives. However, current contraceptive users had lower mean GAP values than either former users or never users. It was therefore concluded that GAP levels alone cannot be used to predict the development of thromboembolic complications in pill users, and that ethinyl estradiol cannot be the main physiological stimulus for GAP synthesis.
Assuntos
Anticoncepcionais Orais Hormonais/toxicidade , Imunoglobulina G/análise , Norgestrel/toxicidade , Tromboembolia/induzido quimicamente , Adulto , Anticoncepcionais Orais Combinados/toxicidade , Feminino , Humanos , Dispositivos Intrauterinos , Masculino , NigériaAssuntos
Etinilestradiol/toxicidade , Diacetato de Etinodiol/toxicidade , Neoplasias Hepáticas Experimentais/induzido quimicamente , Animais , Carcinógenos , Anticoncepcionais Orais Combinados/toxicidade , Anticoncepcionais Orais Sintéticos/toxicidade , Combinação de Medicamentos , Feminino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Ratos , Ratos EndogâmicosRESUMO
Female guinea pigs were given daily doses of a combination of oral contraceptive (OC) agents, consisting of mestranol and norethynodrel suspended in sesame oil or distilled H2O, and were infected in the genital tract with the chlamydial agent of guinea pig inclusion conjunctivitis (GPIC). Counts of chlamydial inclusions in cells of vaginal smears collected during infection, showed prolongation and enhancement of infection in OC-treated animals as compared with controls. Appearance of IgG and IgA antibodies to GPIC in genital secretions, as determined by enzyme-linked immunosorbent assay (ELISA), was also delayed in OC-treated animals as compared with controls. OC-treated infected animals were killed on days 15 and 43, and gross pathological evidence for ascending infection culminating in salpingitis was found in all of five and four of five animals, respectively. On the other hand, among untreated infected controls on each sacrifice day, only one of five animals had any evidence for ascending infection. Chlamydiae were detected by light and electron microscopy in fallopian tube tissue collected on day 15 following OC-treatment but not in tissue from control animals.
Assuntos
Infecções por Chlamydia/patologia , Anticoncepcionais Orais Combinados/toxicidade , Mestranol/toxicidade , Noretinodrel/toxicidade , Salpingite/patologia , Animais , Chlamydia trachomatis/ultraestrutura , Tubas Uterinas/patologia , Feminino , CobaiasAssuntos
Sistema Cardiovascular/efeitos dos fármacos , Anticoncepcionais Orais Combinados/toxicidade , Anticoncepcionais Orais/toxicidade , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Animais , Etinilestradiol/toxicidade , Feminino , Megestrol/análogos & derivados , Megestrol/toxicidade , Acetato de Megestrol , RatosRESUMO
This Memorandum reviews the results of research undertaken in animals and human subjects on the implantable contraceptive, Norplant, and where relevant, its components, levonorgestrel and Silastic. Results from clinical trials, including effectiveness and side-effects, are evaluated and service delivery aspects commented on. The Memorandum concludes with a statement regarding the use of Norplant as an option for long-term reversible contraception.