RESUMO
BACKGROUND Cesarean scar ectopic pregnancy is a rare type of ectopic pregnancy that can result in severe maternal morbidity and mortality. Medical, surgical, and minimally invasive therapies alone or in combination have been described in the literature, but the optimal treatment modality of cesarean scar ectopic pregnancies is unknown. Limited information exists on the course of cesarean scar ectopic pregnancy following treatment with cytotoxic agents. CASE REPORT We present a case of a woman with a history of multiple cesarean births that was provided with medical abortion for an unintended pregnancy. However, upon follow-up, the patient was found to have a cesarean scar ectopic pregnancy. Following the diagnosis, she was treated by multi-dose systemic methotrexate-leucovorin and with ultrasound-guided intra-gestational sac injection of potassium chloride. After resolution of beta human gonadotropin levels, ultrasound follow-up revealed persistence of residual tissue in the cesarean scar. The patient elected for resection of the residual tissue with operative hysteroscopy. We report a novel hysteroscopic finding after medical treatment of a cesarean scar ectopic pregnancy with intra-gestational sac injection of potassium chloride. CONCLUSIONS Direct visualization of the intra-abdominal cavity and intra-uterine cavity showed that combined medical management with systemic methotrexate and local potassium chloride injection is an effective treatment modality for live cesarean scar ectopic pregnancies, with minimal anatomical harm. Hysteroscopic resection offers a safe and effective approach for removal of persistence of residual tissue.
Assuntos
Abortivos não Esteroides , Cesárea , Cicatriz , Metotrexato , Gravidez Ectópica , Humanos , Feminino , Gravidez , Cicatriz/etiologia , Cesárea/efeitos adversos , Metotrexato/uso terapêutico , Adulto , Abortivos não Esteroides/uso terapêutico , Abortivos não Esteroides/administração & dosagem , Cloreto de Potássio/administração & dosagem , Cloreto de Potássio/uso terapêutico , Histeroscopia , Leucovorina/uso terapêuticoRESUMO
OBJECTIVES: Our aims were to examine the prevalence and genetic predictors of aspirin and clopidogrel high on-treatment platelet reactivity (HoTPR), and associated adverse cardiovascular outcomes in patients with peripheral arterial disease (PAD). BACKGROUND: The association of aspirin and clopidogrel HoTPR with outcomes in PAD remains unclear. METHODS: This is a prospective cohort study of patients with angiographically documented PAD involving carotid and lower extremity arteries. Aspirin and clopidogrel HoTPR (using the VerifyNow Assay) and associated genetic predictors were compared to clinical outcomes. The primary end-point was a composite of major adverse cardiovascular events: all-cause mortality, myocardial infarction, stroke, target vessel revascularization (TVR) and limb-loss in patients who underwent extremity intervention. RESULTS: The study was stopped prematurely due to slow patient enrolment. Of 195 patients enrolled, the primary analysis was performed in 154 patients taking both drugs. Aspirin HoTPR was present in 31 (20%) and clopidogrel HoTPR in 76 (49%) patients. There was a trend toward more primary composite outcome events with PRU ≥ 235 (52% freedom-from-event rate vs. 70% for PRU < 235; P = 0.09). TVR was higher in those with PRU ≥ 235 (20 vs. 6%, unadjusted P = 0.02). There was no association between aspirin HoTPR and combined outcomes. Single nucleotide polymorphisms in serum paraoxonase/arylesterase 1 (PON1) gene was associated with aspirin HoTPR (P = 0.005) while SNP in phospholipase A2, group III (PLA2G3) gene was associated with clopidogrel HoTPR (P = 0.002). CONCLUSION: Clopidogrel HoTPR was significantly associated with TVR, while aspirin HoTPR was not associated with adverse clinical outcomes in patients with PAD.
Assuntos
Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Resistência a Medicamentos/genética , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica , Angiografia , Arildialquilfosfatase/genética , Aspirina/efeitos adversos , California/epidemiologia , Clopidogrel/efeitos adversos , Quimioterapia Combinada , Feminino , Fosfolipases A2 do Grupo III/genética , Humanos , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/genética , Inibidores da Agregação Plaquetária/efeitos adversos , Testes de Função Plaquetária , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Ketamine is an anesthetic and a popular abusive drug. As an anesthetic, effects of ketamine on glutamate and GABA transmission have been well documented but little is known about its long-term effects on the dopamine system. In the present study, the effects of ketamine on dopamine were studied in vitro and in vivo. In pheochromocytoma (PC 12) cells and NGF differentiated-PC 12 cells, ketamine decreased the cell viability while increasing dopamine (DA) concentrations in a dose-related manner. However, ketamine did not affect the expression of genes involved in DA synthesis. In the long-term (3 months) ketamine treated mice, significant increases of DA contents were found in the midbrain. Increased DA concentrations were further supported by up-regulation of tyrosine hydroxylase (TH), the rate limiting enzyme in catecholamine synthesis. Activation of midbrain dopaminergic neurons could be related to ketamine modulated cortical-subcortical glutamate connections. Using western blotting, significant increases in BDNF protein levels were found in the midbrain, suggesting that perhaps BDNF pathways in the cortical-subcortical connections might contribute to the long-term ketamine induced TH upregulation. These data suggest that long-term ketamine abuse caused a delayed and persistent upregulation of subcortical DA systems, which may contribute to the altered mental status in ketamine abusers.
Assuntos
Dopamina/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Ketamina/administração & dosagem , Mesencéfalo/efeitos dos fármacos , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Neurônios Dopaminérgicos/metabolismo , Relação Dose-Resposta a Droga , Mesencéfalo/metabolismo , Camundongos , Células PC12 , Ratos , Tirosina 3-Mono-Oxigenase/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
DL-3-n-Butylphthalide (NBP) is a synthetic compound based on L-3-n-Butylphthalide which was isolated from seeds of Apium graveolens. The present study aims at evaluating the outcome of NBP given prior to and after the onset of ischemic stroke in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Stroke was induced by the middle cerebral artery occlusion (MCAO) in SHR and WKY. For pre-treatment, NBP was administered to SHR and WKY daily for two months prior to MCAO. For post-treatment, NBP was given daily for seven consecutive days after MCAO. Seven days post-surgery, rats were tested for the presence of neurological deficits. Magnetic resonance imaging (MRI) and 2,3,5-triphenyltetrazolium chloride (TTC) staining were employed to calculate the infarct volume. The cerebral cortex and corpus striatum in the ischemic penumbra area were examined microscopically for pathological changes. In SHR, NBP pre- and post-treatment significantly lowered neurological deficit scores, reduced infarct volume, and minimized pathological changes in the penumbra area when compared to oil-vehicle treated controls. In WKY, these beneficial effects were observed only in the post-treatment group. The beneficial effects of NBP post-treatment were greater in WKY than in SHR. Results indicated that NBP could exert both preventive and therapeutic effects on ischemic stroke in SHR, but only exerted therapeutic effect in WKY.
Assuntos
Antioxidantes/uso terapêutico , Benzofuranos/uso terapêutico , Lesões Encefálicas/patologia , Lesões Encefálicas/prevenção & controle , Córtex Cerebral/irrigação sanguínea , Doenças do Sistema Nervoso/prevenção & controle , Análise de Variância , Animais , Infarto Encefálico/etiologia , Infarto Encefálico/prevenção & controle , Lesões Encefálicas/etiologia , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Doenças do Sistema Nervoso/etiologia , Exame Neurológico , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Sais de TetrazólioRESUMO
Approximately 80% of smokers initiate tobacco use during adolescence, suggesting that nicotine initiation and nicotine dependence have a substantial age component. There also is a substantial genetic influence on smoking behaviors such as age of initiation and the development of nicotine dependence. The goal of this study was to examine both genetic background and age dependent effects on oral nicotine self-administration and anxiety-like behaviors in mice. Two inbred mouse strains (C3H/Ibg and C57BL/6J) were assessed for oral nicotine preference during early adolescence (postnatal day 24-35), middle adolescence (postnatal day 36-47), late adolescence (postnatal day 48-59), adulthood (postnatal day 60+) and 2 months following their initial exposure to nicotine. Mice also were assessed for innate anxiety using an elevated zero maze to determine if age and/or genetic background influenced anxiety-like behaviors. Results indicated that initial nicotine preference and nicotine preference two months after an initial exposure are both strain and age dependent. Age also had an effect on some baseline anxiety measures but strain differences for most zero maze measures were present throughout all age groups. In general, early adolescent C3H mice exhibited greater nicotine preference while C57 mice displayed greater preference during middle adolescence and upon a second exposure to nicotine. In contrast, C57 mice exhibited reduced anxiety across all ages tested. These studies indicate that genetic background should be considered when evaluating age-dependent effects of drugs of abuse and baseline anxiety-like behaviors.
Assuntos
Envelhecimento , Ansiedade/tratamento farmacológico , Ansiedade/genética , Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Administração Oral , Fatores Etários , Análise de Variância , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Preferências Alimentares/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Nicotina/metabolismo , Agonistas Nicotínicos/metabolismo , Fatores Sexuais , Estatística como AssuntoRESUMO
We studied the mechanism by which the para and meta positional isomers of nitric oxide-donating aspirin (NO-ASA) inhibit human colon cancer cell growth. These compounds are promising chemopreventive agents and represent a broader class of novel drugs. The two isomers differ drastically in their 24-h IC50s for cell growth, which are 12 microM for p-NO-ASA and 230 microM for m-NO-ASA. We examined their effects on cell signaling cascades, including predominantly the mitogen activated protein kinases (MAPKs). The principal differences between the two isomers were: a) p-NO-ASA exerts its effect earlier than m-NO-ASA; b) the predominant effect of m-NO-ASA is on ERK1/2 and Akt; whereas that of p-NO-ASA is on JNK1/2, while both activate p38, with p-NO-ASA showing a stronger and earlier effect; c) ATF-2 is more responsive to m-NO-ASA and c-Jun to p-NO-ASA; d) both isomers seem to have similar effects on AP-1 binding, the main difference between them being the timing of the effect; p-NO-ASA's effect is early and m-NO-ASA's is late; e) p-NO-ASA has an earlier and stronger effect on p21, while m-NO-ASA's effect occurs later and is weaker; and f) cell cycle changes follow the effect on p21 expression. Our findings underscore the role of positional isomerism in modulating the pharmacological effects of drugs and have potentially important implications for the further development of these chemoprevention agents.
Assuntos
Antineoplásicos/farmacologia , Aspirina/análogos & derivados , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Doadores de Óxido Nítrico/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fator 2 Ativador da Transcrição/metabolismo , Antineoplásicos/química , Aspirina/química , Aspirina/farmacologia , Ciclo Celular/efeitos dos fármacos , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Ciclina D1/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Relação Dose-Resposta a Droga , Ativação Enzimática , Células HT29 , Humanos , Concentração Inibidora 50 , Isomerismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Proteína Quinase 9 Ativada por Mitógeno/metabolismo , Doadores de Óxido Nítrico/química , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Interferência de RNA , Transdução de Sinais/genética , Relação Estrutura-Atividade , Fatores de Tempo , Fator de Transcrição AP-1/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Axotomized neurons expressing neuronal nitric oxide synthase (nNOS) may use nitric oxide (NO), known for its antioxidant activities and ability to scavenge free radicals, to protect against oxidative stress. This hypothesis was tested by immunohistochemical examination of superoxide dismutase (SOD) in neurons of the hypoglossal nucleus (HGN) and dorsal motor nucleus of the vagus nerve (DMV) one day to ten weeks after unilateral hypoglossal nerve crush or avulsion combined with vagus nerve crush in adult rats, and also in neurons of the anterior horn (AH) one week after unilateral sciatic nerve crush or avulsion. In the HGN, emergence of nNOS coincided temporally with reduction of CuZn-SOD immunoreactivity (ir), and the level of reduction correlated with that of nNOS induction, differing only in magnitude between nerve crush and nerve avulsion. The two nerve lesion models further revealed the concurrence of nNOS abatement with recovery of CuZn-SOD ir, and absence of nNOS abatement with persistent low CuZn-SOD ir. In the AH, reduced CuZn-SOD ir was localized in the segments containing nNOS positive neurons as a result of sciatic nerve avulsion. CuZn-SOD ir was unchanged in the absence of nNOS induction following sciatic nerve crush. DMV neurons were devoid of CuZn-SOD ir. However, increased Mn-SOD ir one and two weeks post crush was similar to that in HGN neurons. DMV neurons lacked both nNOS abatement and CuZn-SOD ir, which may explain their particular vulnerability to cell death from axotomy in comparison with other peripheral neurons. These data suggest that axotomy-induced nNOS expression is causally linked to oxidative stress, and that NO is neuroprotective, but can become neurodestructive when produced in excess.