RESUMO
The antimicrobial and antibiofilm properties of arginine-based surfactants have been evaluated. These two biological properties depend on both the alkyl chain length and the spacer chain nature. These gemini surfactants exhibit good activity against a wide range of bacteria, including some problematic resistant microorganisms such us methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Moreover, surfactants with a C10 alkyl chain and C3 spacer inhibit the (MRSA) and Pseudomonas aeruginosa biofilm formation at concentrations as low as 8 µg/mL and are able to eradicate established biofilms of these two bacteria at 32 µg/mL. The inhibitory activities of the surfactants over key enzymes enrolled in the skin repairing processes (collagenase, elastase and hyaluronidase) were evaluated. They exhibited moderate anti-collagenase activity while the activity of hyaluronidase was boosted by the presence of these surfactants. These biological properties render these gemini arginine-based surfactants as perfect promising candidates for pharmaceutical and biological properties.
Assuntos
Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Hialuronoglucosaminidase , Anti-Infecciosos/farmacologia , Arginina , Biofilmes , Elastase Pancreática , Pseudomonas aeruginosaRESUMO
This study evaluated the potential of monoolein (MO)-based nanodispersions to promote the cutaneous co-delivery of metformin (MET) and methylene blue (MB) for the treatment of non-melanoma skin cancer. MO-based nanodispersions were obtained using Kolliphor® P407 (KP) and/or sodium cholate (CH), and characterized concerning the structure, thermal stability, ability to disrupt the skin barrier, cutaneous permeation and retention of MB and MET. Additionally, the cytotoxic effect of MO nanodispersions-mediated combination therapy using MET and MB in A431 cells was evaluated. The nanodispersions exhibited nanometric size (<200 nm) and thermal and physical stability. Small angle X-ray scattering studies revealed multiple structures depending on composition. They were able to interact with stratum corneum lipid structure, increasing its fluidity. The effect of MO-nanodispersions on topical/transdermal delivery of MB and MET was composition-dependent. Nanodispersions with low MO content (5 %) and stabilized with KP and CH (0.05-0.10 %) were the most promising, enhancing the cutaneous delivery of MB and MET by 1.9 to 2.2-fold and 1.4 to 1.7-fold, respectively, compared to control. Cytotoxic studies revealed that the most promising MO nanodispersion-mediated combination therapy using MET and MB (1:1) reduced the IC50 by 24-fold, compared to MB solution, and a further reduction (1.5-fold) was observed by MB photoactivation.
Assuntos
Metformina , Azul de Metileno , Administração Cutânea , Azul de Metileno/farmacologia , Pele , Humanos , Linhagem Celular TumoralRESUMO
INTRODUCTION: Acetic acid (AA) has been commonly used in medicine as an antiseptic agent for the past 6000 years. This study evaluated the antibacterial effect of AA during an outbreak in an intensive care unit (ICU) facility in Baja California Sur, México. METHODOLOGY: Thirty-five environmental samples were collected, subsequently, disinfection with AA (4%) was performed, and two days later the same areas were sampled inside the ICU facility. Carbapenem-resistant A. baumannii (CRAB) was detected with loop-mediated isothermal amplification assay (Garciglia-Mercado et al. companion paper), targeting blaOXA-23-like, blaOXA-24-like, blaOXA-51-like, blaOXA-58-like, blaIMP and blaVIM genes. CRAB isolates before and after disinfection were compared by PFGE. RESULTS: Eighteen (54.5%) and five (14.3%) of thirty-five environmental samples were identified as Acinetobacter baumannii before and after disinfection, respectively, showing a significant decrease of 85.7% (p < 0.05) both by Loop-mediated isothermal amplification (LAMP) and polymerase chain reaction (PCR). Furthermore, the presence of blaOXA-23-like and blaOXA-58-like genes significantly decreased (p < 0.05) both by LAMP and PCR methods. PFGE genotype showed high similarity among CRAB isolates before and after disinfection, suggesting wide clonal dissemination in the ICU facility. CONCLUSIONS: This study demonstrated the novel application of AA with the LAMP assays developed for detecting CRAB. AA promises to be a cheap and efficacious disinfectant alternative to both developed and especially developing countries, preventing the spread of this organism in the environment and to other susceptible patients in health care settings.
Assuntos
Ácido Acético/uso terapêutico , Infecções por Acinetobacter/microbiologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Ácido Acético/farmacologia , Acinetobacter baumannii/isolamento & purificação , Antibacterianos/farmacologia , Humanos , Unidades de Terapia Intensiva , México , Testes de Sensibilidade Microbiana , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido NucleicoRESUMO
Cationic amino acid-based surfactants are known to interact with the lipid bilayer of microorganism resulting in cell death through a disruption of the membrane topology. To elucidate the interaction of a cationic surfactant synthesized in our lab, investigations involving Nα-benzoyl-arginine decyl amide (Bz-Arg-NHC10), and model membranes composed by 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) were done. Bz-Arg-NHC10was able to penetrate into DPPC monolayers up to a critical pressure of 59.6 mN m-1. Differential scanning calorimetry revealed that as the concentration of Bz-Arg-NHC10 increased, the main transition temperature of DPPC slightly decreased. Atomic force microscopy (AFM) in situ experiments performed on supported DPPC bilayers on mica allowed monitoring the changes induced by Bz-Arg-NHC10. DPPC bilayer patches were partially removed, mainly in borders and bilayer defects for 50 µM Bz-Arg-NHC10 solution. Increasing the concentration to 100 µM resulted in a complete depletion of the supported bilayers. Surface plasmon resonance (SPR) experiments, carried out with fully DPPC bilayers covered chips, showed a net increase of the SPR signal, which can be explained by Bz-Arg-NHC10 adsorption. When patchy DPPC bilayers were formed on the substrate, a SPR signal net decrease was obtained, which is consistent with the phospholipids' removal observed in the AFM images. The results obtained suggest that the presence of the benzoyl group attached to the polar head of our compound would be the responsible of the increased antimicrobial activity against gram-negative bacteria when compared with other arginine-based surfactants.
Assuntos
1,2-Dipalmitoilfosfatidilcolina/química , Arginina/análogos & derivados , Bicamadas Lipídicas/química , Tensoativos/química , Adsorção , Arginina/química , Varredura Diferencial de Calorimetria , Cátions/química , Interações Hidrofóbicas e Hidrofílicas , Membranas Artificiais , Microscopia de Força Atômica , Ressonância de Plasmônio de SuperfícieRESUMO
The aim of this study was to develop an HPLC method for simultaneous quantification of metformin (MET) and methylene blue (MB) in in vitro skin permeation/retention studies, in which retention was evaluated in the different layers of the skin [stratum corneum (SC) and the viable epidermis + dermis (VE + D)]. The method was validated considering the following parameters: specificity, linearity, quantitation limit (LOQ), recovery, precision and accuracy. Calibration curves were obtained using the following six matrices: methanol, water, methanolic extracts from the SC and VE + D spiked with the drugs and drugs extracted from the SC and VE + D. The precision, accuracy and LOQ of the method were evaluated in water and in VE + D and SC, applying the drug extraction process. The results show that the method is selective and linear for both drugs. The precision and accuracy values, independent of matrix and drug, were below the limit of 15%. The LOQ of MB was defined as 0.4 µg/ml in the VE + D and SC and 0.8 µg/ml in water. The LOQ of MET was defined as 0.8 µg/ml in the VE + D and SC and 0.4 µg/ml in the water. The recovery of the method was adequate, consistent and reproducible for the concentration range of 0.4-10 µg/ml for MB (73.3-92.1%) and 0.8-10.0 µg/mL for MET (72.4-94.4%). This method has a potential application in the development of formulation for skin delivery of MB and MET.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Metformina/análise , Azul de Metileno/análise , Absorção Cutânea/fisiologia , Pele/química , Animais , Modelos Lineares , Metformina/farmacocinética , Azul de Metileno/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Pele/metabolismo , SuínosRESUMO
INTRODUCTION: Carbapenem-resistant A. baumannii (CRAB) represents a public health threat increasing worldwide. We assess the suitability of a loop-mediated isothermal amplification (LAMP) method for on-site screening of CRAB in a hospital facility. METHODOLOGY: A set of six primers were designed for recognizing eight distinct sequences on six targets: blaOXA-23-like, blaOXA-24-like, blaOXA-51-like, blaOXA-58-like, blaIMP, and blaVIM. A LAMP method was developed, optimized and evaluated for the identification of CRAB in thirty-three environmental samples from an outbreak in an Intensive Care Unit (ICU) facility. RESULTS: The sensitivity of the LAMP assay for the detection of A. baumannii was ten-fold higher than the PCR assay (1.0 ng.µL-1). The LAMP assays showed a higher detection rate for CRAB samples and robust diagnosis performance in comparison to a conventional PCR, with clinical sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 100% for blaOXA-23-like, blaOXA-51-like and blaVIM. CONCLUSIONS: The developed LAMP assays are powerful tools that can be useful in on-site screening of CRAB causing local outbreaks in clinics and hospitals facilities where costs and equipment restraints are imperative.
Assuntos
Infecções por Acinetobacter/diagnóstico , Acinetobacter baumannii/isolamento & purificação , Surtos de Doenças , Farmacorresistência Bacteriana , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Infecção Hospitalar/microbiologia , Hospitais/estatística & dados numéricos , Humanos , México , Testes de Sensibilidade Microbiana , Valor Preditivo dos Testes , Sensibilidade e EspecificidadeRESUMO
Toluene is a widely misused solvent that causes a variety of behavioral effects in both humans and animals. Preclinical and clinical research has provided evidence that toluene inhalation produces psychoactive effects similar to those caused by other Central Nervous System depressant drugs, but little is known about the consequences of inhaling solvents other than toluene that are also present in commercial products. As part of this research project, we studied the effects of hydrocarbon solvents chemically related to toluene on anxiety-like behavior, passive-avoidance learning, nociception, motor coordination and social interaction. We tested independent groups of adolescent male Wistar rats in the burying behavior task, step through avoidance learning task, hot plate test, shock threshold test, social interaction or rotarod tests after a 30â¯min exposure to either cyclohexane, benzene, toluene or m-xylene (2000 to 8000â¯ppm). Control animals breathed only air. Benzene, toluene and m-xylene produced anxiolytic-like actions, impaired learning, caused antinociception and decreased social interaction in a concentration-dependent manner. Locomotor coordination was impaired only with 8000â¯ppm m-xylene and 8000â¯ppm toluene. Cyclohexane had no effect on any of the behavioral tasks. Our data suggest that the aromatic ring is critical for solvents to produce a wide variety of behavioral effects.
Assuntos
Comportamento Animal/efeitos dos fármacos , Benzeno/toxicidade , Cicloexanos/toxicidade , Solventes/toxicidade , Tolueno/toxicidade , Xilenos/toxicidade , Animais , Ansiedade/induzido quimicamente , Aprendizagem da Esquiva/efeitos dos fármacos , Masculino , Atividade Motora/efeitos dos fármacos , Nociceptividade/efeitos dos fármacos , Ratos , Ratos Wistar , Comportamento SocialRESUMO
PURPOSE: To evaluate if the duration of epilepsy influences MRI volumes of the hippocampus, amygdala, parahippocampal gyrus, entorhinal cortex and temporal pole of both hemispheres and epileptogenic hippocampus neuronal cell density and dentate gyrus granular cells distribution in patients with refractory mesial temporal lobe epilepsy due to hippocampal sclerosis (MTLE/HS). METHODS: Seventy-seven patients with refractory MTLE/HS submitted to surgery were included. Histopathological analysis included: (1) quantitative: hippocampal subfields and total estimated hippocampal cell density (HCD), thickness of the dentate gyrus - normal, thinning or dispersion; (2) qualitative: type of HS and granule cells pathology in the dentate gyrus (normal, neuronal cell loss, dispersion and bilamination). Automated MRI-derived measurements from bilateral temporal structures (hippocampus, amygdala, parahippocampal gyrus, temporal pole, entorhinal cortex) were obtained for 58 subjects. Histopathological and imaging findings were compared with data from specimens obtained in autopsies of age-matched individuals and living controls, respectively, and the data were adjusted for the age at epilepsy onset and the frequency of focal impaired awareness seizures/month. RESULTS: Forty-two (54.5%) patients presented right HS. The greater the duration of epilepsy, the smaller the total estimated HCD (p = 0.025; r = -0.259). Patients with a normal distribution of the granular cells had a shorter epilepsy duration than those with dispersion (p = 0.018) or thinning (p = 0.031). A reduced ipsilateral hippocampal volume (r = -0.551, p = 0.017) and a smaller hippocampal asymmetry index (r = -0.414, p = 0.002) were correlated to a longer epilepsy duration. The estimated HCD was correlated to the volume of the ipsilateral hippocampus (r = 0.420, p = 0.001). CONCLUSION: Our study showed an increasing atrophy of the ipsilateral hippocampus in patients with a longer epilepsy duration. Our data suggest that this reduction in hippocampal volume is related to neuronal loss. Besides that, we also showed an increased probability of exhibiting an abnormal distribution of the granular cells in the dentate gyrus in patients with longer epilepsy duration.
Assuntos
Mapeamento Encefálico , Encéfalo/patologia , Epilepsia do Lobo Temporal/patologia , Hipocampo/patologia , Neurônios/metabolismo , Adolescente , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Contagem de Células , Epilepsia do Lobo Temporal/complicações , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neurônios/patologia , Fosfopiruvato Hidratase/metabolismo , Esclerose/diagnóstico por imagem , Esclerose/patologia , Adulto JovemRESUMO
It is critical to develop an effective understanding of the interaction between the drug, delivery system and skin in order to predict and assess skin penetration and permeation. Experimental models for the assessment of topical and transdermal delivery systems must permit evaluation of these complex interactions. Whilst in the past, animal models were commonly used, recent regulatory guidelines, based on 3R principles (refinement, reduction, replacement), encourage the rational use of animals. Alternative methods have been proposed for use in the development of topical and transdermal delivery systems which are often used in combination. We will review the current state of the art in alternative methods for topical and transdermal delivery systems development, including technologies that can assist in the characterization of skin penetration/permeation studies.
Assuntos
Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas/administração & dosagem , Pele/efeitos dos fármacos , Administração Cutânea , Animais , HumanosRESUMO
OBJECTIVE: The objectives of this study were to verify in a series of patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) if those with low intellectual quotient (IQ) levels have more extended areas of atrophy compared with those with higher IQ levels and to analyze whether IQ could be a variable implicated on a surgical outcome. MATERIAL AND METHODS: Patients (n=106) with refractory MTLE-HS submitted to corticoamygdalohippocampectomy (CAH) (57 left mesial temporal lobe epilepsy (MTLE); 45 males) were enrolled. To determine if the IQ was a predictor of seizure outcome, totally seizure-free (SF) versus nonseizure-free (NSF) patients were evaluated. FreeSurfer was used for cortical thickness and volume estimation, comparing groups with lower (<80) and higher IQ (90-109) levels. RESULTS: In the whole series, 42.45% of patients were SF (Engel Class 1a; n=45), and 57.54% were NSF (n=61). Total cortical volume was significantly reduced in the group with lower IQ (p=0.01). Significant reductions in the left hemisphere included the following: rostral middle frontal (p=0.001), insula (p=0.002), superior temporal gyrus (p=0.003), thalamus (p=0.004), and precentral gyrus (p=0.02); and those in the right hemisphere included the following: rostral middle frontal (p=0.003), pars orbitalis (p=0.01), and insula (p=0.02). Cortical thickness analysis also showed reductions in the right superior parietal gyrus in patients with lower IQ. No significant relationship between IQ and seizure outcome was found. CONCLUSIONS: This is the first study of a series of patients with pure MTLE-HS, including those with low IQ and their morphometric magnetic resonance imaging (MRI) features using FreeSurfer. Although patients with lower intellectual scores presented more areas of brain atrophy, IQ was not a predictor of surgical outcome. Therefore, when evaluating seizure follow-up, low IQ in patients with MTLE-HS might not contraindicate resective surgery.
Assuntos
Epilepsia do Lobo Temporal/cirurgia , Hipocampo/patologia , Deficiência Intelectual/patologia , Esclerose/patologia , Adolescente , Adulto , Atrofia/patologia , Córtex Cerebral/patologia , Epilepsia do Lobo Temporal/patologia , Feminino , Lobo Frontal/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Análise de Regressão , Convulsões/patologia , Lobo Temporal/patologia , Tálamo/patologia , Resultado do Tratamento , Adulto JovemRESUMO
Histiocytoses are rare diseases caused by the proliferation of histiocytes. The pathogenesis remains unknown and the highest incidence occurs in pediatric patients. The clinical presentations can be varied, in multiple organs and systems, and the skin lesions are not always present. Evolution is unpredictable and treatment depends on the extent and severity of the disease. It is described the case of a patient with various neurological symptoms, extensively investigated, who had its was diagnosed with histiocytosis from a single skin lesion. This report highlights the importance of Dermatology in assisting the investigation of difficult cases in medical practice.
Assuntos
Histiocitose de Células de Langerhans/patologia , Dermatopatias/patologia , Pele/patologia , Doenças Ósseas/diagnóstico por imagem , Encefalopatias/diagnóstico por imagem , Granuloma Eosinófilo/diagnóstico por imagem , Granuloma Eosinófilo/patologia , Evolução Fatal , Histiocitose de Células de Langerhans/diagnóstico por imagem , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
Abstract: Histiocytoses are rare diseases caused by the proliferation of histiocytes. The pathogenesis remains unknown and the highest incidence occurs in pediatric patients. The clinical presentations can be varied, in multiple organs and systems, and the skin lesions are not always present. Evolution is unpredictable and treatment depends on the extent and severity of the disease. It is described the case of a patient with various neurological symptoms, extensively investigated, who had its was diagnosed with histiocytosis from a single skin lesion. This report highlights the importance of Dermatology in assisting the investigation of difficult cases in medical practice.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Pele/patologia , Dermatopatias/patologia , Histiocitose de Células de Langerhans/patologia , Doenças Ósseas/diagnóstico por imagem , Encefalopatias/diagnóstico por imagem , Espectroscopia de Ressonância Magnética , Granuloma Eosinófilo/patologia , Granuloma Eosinófilo/diagnóstico por imagem , Histiocitose de Células de Langerhans/diagnóstico por imagem , Evolução FatalRESUMO
La hiperprolactinemia es uno de los trastornos neuroendocrinológicos más frecuentes; la causa común de la hiperprolactinemia es la presencia de un adenoma hipofisario productor de prolactina o prolactinoma. El país cuenta con escasa referencia bibliográfica sobre la patología presentada, por lo que resulta importante realizar la exposición de este caso. Objetivo: documentar el abordaje de hiperprolactinemia en el país. Caso clínico: paciente femenina de 22 años, con antecedentes familiares de macroprolactinoma; se presenta con historia de amenorrea de 6 años y caída de cabello de 2 años de evolución; prurito intenso en ambas mamas con predominio en la areola derecha desde hace 1 año; alteraciones en los niveles de prolactina presentando valores de 33.5ng/mL y ultrasonografía abdominal ausente de anormalidades. Tratada con cabergolina, sin éxito evidente en el tratamiento. Conclusión: en pacientes con hiperprolactinemia, su abordaje debe hacerse de manera ordenada, integral, secuencial y detallada con el fin de descartar previo al tratamiento, situaciones que secundariamente elevan los valores de prolactina. Esto lo demuestra el caso expuesto donde se integran diferentes pruebas clínicas y laboratoriales para descartar la etiología de la hiperprolactinemia en el país...(AU)
Assuntos
Humanos , Feminino , Adulto , Adenoma Hipofisário Secretor de ACT , Doenças do Sistema Endócrino , Hiperprolactinemia , Prolactinoma/complicaçõesRESUMO
Progesterone synthesis in human placenta is essential to maintain pregnancy. The limiting step in placental progesterone synthesis is cholesterol transport from the cytoplasm to the inner mitochondrial membrane. Multiple proteins located in mitochondrial contact sites seem to play a key role in this process. Previously, our group identified the heat shock protein 60 (HSP60) as part of mitochondrial contact sites in human placenta, suggesting its participation in progesterone synthesis. Here, we examined the role of HSP60 in progesterone synthesis. Our results show that over-expression of HSP60 in human placental choriocarcinoma cells (JEG-3) and human embryonic kidney 293 cells (HEK293) promotes progesterone synthesis. Furthermore, incubation of the HSP60 recombinant protein with intact isolated mitochondria from JEG-3 cells also promotes progesterone synthesis in a dose-related fashion. We also show that HSP60 interacts with STARD3 and P450scc proteins from mitochondrial membrane contact sites. Finally, we show that the HSP60 recombinant protein binds cholesterol. Ours results demonstrate that HSP60 participates in mitochondrial progesterone synthesis. These findings provide novel insights into progesterone synthesis in the human placenta and its role in maintaining pregnancy.
Assuntos
Chaperonina 60/metabolismo , Regulação da Expressão Gênica/fisiologia , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Progesterona/biossíntese , Linhagem Celular , Chaperonina 60/genética , Colesterol , Feminino , Humanos , Proteínas Mitocondriais/genética , Placenta/citologia , Gravidez , Ligação ProteicaRESUMO
It is known the deleterious effects of diabetes on embryos, but the effects of diabetes on placenta and its mitochondria are still not well known. In this work we generated a mild hyperglycemia model in female wistar rats by intraperitoneal injection of streptozotocin in 48 hours-old rats. The sexual maturity onset of the female rats was delayed around 6-7 weeks and at 16 weeks-old they were mated, and sacrificed at day 19th of pregnancy. In placental total tissue and isolated mitochondria, the fatty acids composition was analyzed by gas chromatography, and lipoperoxidation was measured by thiobarbituric acid reactive substances. Membrane fluidity in mitochondria was measured with the excimer forming probe dipyrenylpropane and mitochondrial function was measured with a Clark-type electrode. The results show that even a chronic mild hyperglycemia increases lipoperoxidation and decreases mitochondrial function in placenta. Simultaneously, placental fatty acids metabolism in total tissue is modified but in a different way than in placental mitochondria. Whereas the chronic mild hyperglycemia induced a decrease in unsaturated to saturated fatty acids ratio (U/S) in placental total tissue, the ratio increased in placental mitochondria. The measurements of membrane fluidity showed that fluidity of placenta mitochondrial membranes increased with hyperglycemia, showing consistency with the fatty acids composition through the U/S index. The thermotropic characteristics of mitochondrial membranes were changed, showing lower transition temperature and activation energies. All of these data together demonstrate that even a chronic mild hyperglycemia during pregnancy of early reproductive Wistar rats, generates an increment of lipoperoxidation, an increase of placental mitochondrial membrane fluidity apparently derived from changes in fatty acids composition and consequently, mitochondrial malfunction.
Assuntos
Hiperglicemia/metabolismo , Hiperglicemia/patologia , Peroxidação de Lipídeos , Peróxidos Lipídicos/metabolismo , Fluidez de Membrana , Mitocôndrias/metabolismo , Placenta/patologia , Animais , Glicemia/metabolismo , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Feminino , Hiperglicemia/sangue , Masculino , Membranas Mitocondriais/metabolismo , Gravidez , Ratos , Ratos Wistar , Maturidade SexualRESUMO
UNLABELLED: Hemoperitoneum is a rare cause of acute abdomen, which is usually due to liver, spleen, hematologic and vascular causes. We should consider gynecological origin in women in reproductive age, being a rare etiology in postmenopausal. CLINICAL CASE: We report the case of a spontaneous hemoperitoneum in a postmenopausal woman as the first manifestation of an ovarian tumor, with exceptional pathological lineage: clear cell carcinoma. Hemoperitoneum is a suspected diagnosis before clinical symptoms of hypovolemic shock and acute abdomen, with decrease in hemoglobin. To treating underlying cause, which in this case was surgical, it's important the clinical suspect and the appropriate hemodynamic support of the patient. Despite the resolution of the acute, it is particularly important the subsequent clinical monitoring of the patient by the peculiarities of this type of tumors.
Assuntos
Hemoperitônio/etiologia , Neoplasias Ovarianas/complicações , Idoso , Feminino , Humanos , Neoplasias Ovarianas/diagnósticoRESUMO
To achieve an efficient skin penetration of most compounds it is necessary to overcome the barrier function of the skin, provided mainly (but not only) by the stratum corneum. Among various strategies used or studied to date, chemical penetration enhancers are the most frequently employed with one of the longest histories of use. There is a multitude of agents described as penetration enhancers, and they present varying properties and structures. In this manuscript, we aim to provide a brief overview of traditional enhancers and some of their properties, focusing on the benefits of combination of chemical enhancers and on selected novel compounds that have shown promise to increase drug delivery into/across the skin.
Assuntos
Excipientes/química , Absorção Cutânea/efeitos dos fármacos , Administração Cutânea , Animais , Sistemas de Liberação de Medicamentos , Excipientes/efeitos adversos , HumanosRESUMO
BACKGROUND: The rectovaginal fistula is a rare disease whose treatment is extremely difficult. OBJECTIVE: To present the expectant management of rectovaginal fistula as an alternative to surgery for those cases in which the surgical risk is not an acceptable option. CLINICAL CASE: We report the case of a rectovaginal fistula in an 85-year-old woman with significant comorbidity that avoided the performance of any surgical technique. CONCLUSION: In patients whose surgical risk does not exceed the benefits, non-surgical management would be an option of treatment of rectovaginal fistula.
Assuntos
Fístula Retovaginal/terapia , Idoso de 80 Anos ou mais , Feminino , Humanos , Fístula Retovaginal/patologia , Risco , Resultado do TratamentoRESUMO
RATIONALE: Toluene is a misused inhalant with hallucinogenic properties and complex effects. Toluene blocks N-methyl-D-aspartate (NMDA) receptors, releases dopamine (DA), and modifies several neurotransmitter levels; nonetheless, the mechanism by which it produces hallucinations is not well characterized. OBJECTIVES: This study aims (a) to study toluene's effects on the 5-HT2A-mediated head-twitch response (HTR), dopamine (DA), and serotonin (5-HT) tissue levels in discrete brain regions; (b) to compare the actions of toluene, ketamine, and 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) on HTR; and (c) to study the pharmacological blockade of toluene's and ketamine's effects by selective drugs. METHODS: Independent groups of rats inhaled toluene (500-12,000 ppm) for 30 min during which the occurrence of serotonergic signs was analyzed. Brains were obtained after exposure to determine DA and 5-HT levels by HPLC. RESULTS: Toluene concentration-dependently induced HTR. Other serotonin syndrome signs were evident at high concentrations. Toluene (4000 and 8000 ppm), and ketamine (3 and 10 mg/kg), significantly increased 5-HT levels in the frontal cortex (FC) striatum, hippocampus, and brain stem, as well as DA levels in the striatum and FC. Pretreatment with ketanserin (5HT2A/2C receptor antagonist), M100907 (selective 5-HT2A receptor antagonist), D-serine (co-agonist of the NMDA receptor glycine site), and haloperidol (D2 receptor antagonist) significantly decreased toluene's and ketamine's actions. The 5HT1A receptor antagonist WAY100635 had no effect. CONCLUSION: Toluene stimulates 5HT2A and 5HT2C receptors, and increases 5-HT and DA levels. These actions are similar to those produced by ketamine and involve activation of a complex neurotransmitter network that includes NMDA receptor antagonism.