RESUMO
Data presented in this article focused on the application of Methyl Ester Sulphonate (MES) surfactant and nanopolystyrene in water based drilling fluid. Data from rheology study using Bingham and Power law models showed that the synergy of MES and nanopolystyrene improved the formulated drilling fluid. Filtration study under LPLT and HPHT conditions showed that MES and nanopolystyrene drilling fluid reduced filtration loss by 50.7% at LPLT and 61.1% at HPHT conditions. These filtration data were validated by filter cake permeability and scanning electron microscope images.
RESUMO
The majority of previous work examining stress responses has been done in males. Recently, it has become clear that the impact of stressor exposure is modulated by sex. One stress response that may be affected by sex is the induction of intracellular heat shock protein (HSP) 72, which is a stress- responsive molecular chaperone that refolds denatured proteins and promotes cellular survival. The following study compared HSP72 in males and females and also examined whether the estrous cycle altered HSP72 induction in females. We hypothesized that females compared with males would have a constrained HSP72 response after an acute stressor and that the stress-induced HSP72 response in females would fluctuate with the estrous cycle. Male and female F344 rats were either left in their home cage or exposed to acute tail-shock stress (8-10/group). Immediately following stressor, trunk blood was collected and tissues were flash frozen. Vaginal smear and estrogen enzyme immunoassay were used to categorize the phase of estrous. Results show that female rats had a greater corticosterone response than males, that both males and females exhibit a stress-induced release of progesterone, and that males and females had equal levels of stress-induced circulating norepinephrine. Sexual dimorphism of the HSP72 (ELISA) response existed in pituitary gland, mesenteric lymph nodes, and liver such that female rats had an attenuated HSP72 response compared with males after stress. The adrenal glands, spleen, and heart did not exhibit sexual dimorphism of the HSP72 response. The estrous cycle did not have a significant effect on basal or stress-induced HSP72 in females.
Assuntos
Regulação da Expressão Gênica/fisiologia , Proteínas de Choque Térmico HSP72/metabolismo , Caracteres Sexuais , Estresse Fisiológico/fisiopatologia , Corticosteroides/sangue , Glândulas Suprarrenais/metabolismo , Animais , Ensaio de Imunoadsorção Enzimática , Estrogênios/sangue , Ciclo Estral/fisiologia , Feminino , Proteínas de Choque Térmico HSP72/genética , Fígado/metabolismo , Linfonodos/metabolismo , Masculino , Músculo Esquelético/metabolismo , Miocárdio/metabolismo , Norepinefrina/sangue , Hipófise/metabolismo , Progesterona/sangue , Ratos , Baço/metabolismo , Estresse Fisiológico/genéticaRESUMO
Proinflammatory cytokines act at receptors in the CNS to alter physiological and behavioral responses. Exposure to stressors increases both peripheral and central proinflammatory cytokines, yet the mechanism(s) of induction remain unknown. Experiments here examined the role of catecholamines in the in vivo induction of proinflammatory cytokines following tailshock stress. Rats were pretreated i.p. with 2.0 mg/kg prazosin (alpha1-adrenoceptor antagonist), 10.0 mg/kg propranolol (beta-adrenoceptor antagonist), or 5.0 mg/kg labetalol (alpha1- and beta-adrenoceptor antagonist) 30 min prior to tailshock exposure and plasma interleukin-1beta (IL-1beta) and IL-6, along with tissue interleukin-1beta from the hypothalamus, hippocampus, and pituitary were measured immediately following stressor termination. Prazosin attenuated stress-induced plasma IL-1beta and IL-6, but had no effect on tissue IL-1beta levels, while propranolol attenuated plasma IL-6 and blocked tissue IL-1beta elevation, and labetalol, which cannot cross the blood-brain barrier, attenuated plasma IL-1beta and IL-6, blocked pituitary IL-1beta, but had no effect on central tissue IL-1beta levels. Furthermore, administration of 50.0 mg/kg N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride, a neurotoxin that lesions neural projections from the locus coeruleus, prevented stress-induced elevation in hippocampal IL-1beta, a region highly innervated by the locus coeruleus, but had no effect on hypothalamic IL-1beta, a region that receives few locus coeruleus projections. Finally, i.p. injection of 5.0 mg/kg isoproterenol (beta-adrenoceptor agonist) was sufficient to induce circulating IL-1 and IL-6, and tissue IL-1beta. These data suggest catecholamines play an important role in the induction of stress-induced proinflammatory cytokines and that beta-adrenoceptors are critical for tissue IL-1beta induction, while both alpha- and beta-adrenoceptors contribute to the induction of plasma cytokines.
Assuntos
Química Encefálica , Catecolaminas/metabolismo , Citocinas/metabolismo , Estresse Psicológico/fisiopatologia , Antagonistas Adrenérgicos alfa/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Química Encefálica/efeitos dos fármacos , Catecolaminas/análise , Citocinas/análise , Eletrochoque , Imuno-Histoquímica , Labetalol/farmacologia , Masculino , Prazosina/farmacologia , Propranolol/farmacologia , Ratos , Ratos Endogâmicos F344 , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Exposure to an intense acute stressor immediately following immunization leads to a reduction in anti-KLH IgM, IgG, and IgG2a, but not IgG1. Stress also depletes splenic norepinephrine (NE) content. Immunization during pharmacological (alpha-methyl-p-tyrosine) or stress-induced splenic NE depletion results in antibody suppression similar to that found in rats immunized prior to stressor exposure. Prevention of splenic NE depletion during stress by tyrosine, but not pharmacological elevation (mirtazapine) of NE, resulted in normal antibody responses. These data support the hypothesis that splenic NE depletion is necessary and sufficient for stress-induced suppression of antibody to a T-cell dependent antigen.
Assuntos
Imunoglobulina G , Imunoglobulina M , Terapia de Imunossupressão , Norepinefrina/antagonistas & inibidores , Norepinefrina/metabolismo , Baço/imunologia , Baço/metabolismo , Estresse Fisiológico/imunologia , Estresse Fisiológico/metabolismo , Animais , Catecolaminas/biossíntese , Hemocianinas/administração & dosagem , Hemocianinas/imunologia , Imunoglobulina G/biossíntese , Imunoglobulina G/metabolismo , Imunoglobulina M/biossíntese , Imunoglobulina M/metabolismo , Terapia de Imunossupressão/métodos , Injeções Intraperitoneais , Masculino , Metiltirosinas/administração & dosagem , Mianserina/administração & dosagem , Mianserina/análogos & derivados , Mirtazapina , Ratos , Ratos Endogâmicos F344 , Estresse Fisiológico/fisiopatologia , Fatores de Tempo , Tirosina/administração & dosagemRESUMO
Converging lines of evidence implicate the beta-amyloid peptide (Ass) as causative in Alzheimer's disease. We describe a novel class of compounds that reduce A beta production by functionally inhibiting gamma-secretase, the activity responsible for the carboxy-terminal cleavage required for A beta production. These molecules are active in both 293 HEK cells and neuronal cultures, and exert their effect upon A beta production without affecting protein secretion, most notably in the secreted forms of the amyloid precursor protein (APP). Oral administration of one of these compounds, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester, to mice transgenic for human APP(V717F) reduces brain levels of Ass in a dose-dependent manner within 3 h. These studies represent the first demonstration of a reduction of brain A beta in vivo. Development of such novel functional gamma-secretase inhibitors will enable a clinical examination of the A beta hypothesis that Ass peptide drives the neuropathology observed in Alzheimer's disease.
Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Dipeptídeos/administração & dosagem , Endopeptidases/metabolismo , Administração Oral , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Secretases da Proteína Precursora do Amiloide , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Ácido Aspártico Endopeptidases , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Endopeptidases/efeitos dos fármacos , Inibidores Enzimáticos/administração & dosagem , Feminino , Humanos , Injeções Subcutâneas , Rim/citologia , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fragmentos de Peptídeos/metabolismoRESUMO
The purpose of this study was to examine the effect of acute (24 h) and chronic (5 wk) hypobaric hypoxic exposure equivalent to a simulated altitude of 4,300 m (446 mmHg) on the enzymes of fat metabolism. Heart, liver, and skeletal muscle were taken from 32 male Sprague-Dawley rats. Altitude exposure did not affect the activity of citrate synthase in any of the tissues, suggesting that mitochondrial content was unchanged. Carnitine palmitoyltransferase-I (CPT-I) activity was significantly reduced in the heart by both acute and chronic high altitude exposure compared with controls. A similar reduction was found for CPT-I activity in extensor digitorum longus after acute and chronic exposure compared with control animals. CPT-I activity was not affected by altitude exposure in the soleus muscle or the liver. 3-Hydroxyacyl-CoA dehydrogenase (beta-HAD) activity was significantly depressed in the hearts of chronically exposed animals compared with controls. No difference between acute and control animals was found in the heart for beta-HAD activity. Liver beta-HAD activity was also significantly decreased in the acclimatized as well as in the acute animals compared with the control group. Quadriceps beta-HAD activity was reduced for the chronic animals only compared with controls. These data suggest that acclimatization to high altitude selectively decreases key enzymes in fat utilization and oxidation in the heart, liver, and select skeletal muscles.
Assuntos
3-Hidroxiacil-CoA Desidrogenases/metabolismo , Altitude , Carnitina O-Palmitoiltransferase/metabolismo , Metabolismo dos Lipídeos , Animais , Citrato (si)-Sintase/metabolismo , Fígado/metabolismo , Masculino , Músculo Esquelético/metabolismo , Miocárdio/metabolismo , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
At the heart of the debate over assisted suicide is the recognition that not all persons can be healed and not all suffering can be relieved. This article addresses the ethical, professional and legal issues to be considered by the nurses in the United States who are facing patients' requests for assisted suicide. Both personal and professional risks, and the consequences of an action must be evaluated. Ultimately, a decision is based on some ranking of patient values; personal values and beliefs; professional codes, standards and other guidelines; and societal laws and regulations.
Assuntos
Ética em Enfermagem , Defesa do Paciente , Suicídio Assistido , Beneficência , Regulamentação Governamental , Humanos , Futilidade Médica , Competência Mental , Papel do Profissional de Enfermagem , Defesa do Paciente/legislação & jurisprudência , Autonomia Pessoal , Medição de Risco , Sociedades de Enfermagem , Suicídio Assistido/legislação & jurisprudência , Estados UnidosRESUMO
OBJECTIVE: There is a current debate whether multicentric osteosarcoma represents synchronous multiple primary osteosarcomas or metastatic disease. The purpose of this report is to evaluate the etiology, presentation, and classification of this entity. DESIGN AND PATIENTS: Six patients ranging in age from 7 to 29 years were studied. The clinical, radiographic, and pathologic findings are reported. In addition, a review of the literature was undertaken. RESULTS: The clinical courses of our six patients as well as a review of the literature suggest that multicentric osteosarcoma represent one extreme of a continuous scale of metastatic osteosarcoma rather than multiple synchronous primary tumors. The presentation is unusual and the clinical behavior distinctive, but the mechanism of spread remains the same: blood-borne and lymphatic-borne. CONCLUSIONS: Our experience with these six patients supports the concept in the recent literature that synchronous osteosarcoma is one extreme of the spectrum of metastatic osteosarcoma. Its unique features are: (1) multiple radiodense lesions that present simultaneously with or without pulmonary metastases; (2) a single "dominant" lesion with multiple smaller lesions; and (3) a uniformly rapid, fatal prognosis. Osteosarcoma should be regarded as a metastatic disease, even when only a single primary lesion is found at the initial presentation.
Assuntos
Neoplasias Ósseas/patologia , Neoplasias Pulmonares/secundário , Neoplasias Primárias Múltiplas , Osteossarcoma/patologia , Adolescente , Adulto , Neoplasias Ósseas/diagnóstico por imagem , Criança , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Metástase Linfática , Imageamento por Ressonância Magnética , Masculino , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/secundário , Tomografia Computadorizada por Raios XRESUMO
Neuropeptide Y (NPY), which is found in high concentrations in several regions of the brain including nuclei of the brain stem and in nerve fibers surrounding cerebral vessels, has been proposed to play a role in regulating cerebral blood flow (CBF) and systemic vegetative functions. Since CBF is altered during meningitis, we examined whether NPY concentrations changed in various regions of the rabbit brain in response to experimental pneumococcal meningitis. Changes were most pronounced in the medulla, where NPY concentration increased threefold after 48 h of infection. Concomitantly, there was an increase in NPY immunoreactive fibers surrounding small vessels in the dorsolateral medulla, especially in the nucleus tractus solitarius. These results suggest that NPY may play a role in inducing some of the hemodynamic changes seen during pneumococcal meningitis.
Assuntos
Química Encefálica/fisiologia , Meningite Pneumocócica/metabolismo , Neuropeptídeo Y/metabolismo , Animais , Glucose/metabolismo , Imuno-Histoquímica , Lactatos/sangue , Ácido Láctico , Bulbo/metabolismo , Neuropeptídeo Y/líquido cefalorraquidiano , Coelhos , RadioimunoensaioRESUMO
To identify neurotoxic factors in meningitis, a neuronal cell line (HN33.1) was exposed to cerebrospinal fluid (CSF) obtained from rabbits with pneumococcal meningitis or Escherichia coli meningitis or 2 h and 6 h after meningitis was induced by proinflammatory bacterial products (pneumococcal cell walls, endotoxin). CSF from all types of meningitis induced similar degrees of cytotoxicity. When a soluble tumor necrosis factor (TNF) receptor that completely blocked TNF-mediated toxicity at 10(-7) M was used, all toxicity in meningitis caused by E. coli, endotoxin, or pneumococcal cell wall administration (2 h afterwards) was mediated by TNF. In contrast, CSF from animals with meningitis caused by live pneumococci or pneumococcal cell wall injection (6 h afterwards) retained cytotoxicity in the presence of the TNF receptor. Thus, in established pneumococcal meningitis, but not in the other forms of meningitis, TNF is not the only component toxic in this neuronal cell line.
Assuntos
Líquido Cefalorraquidiano/fisiologia , Escherichia coli , Meningites Bacterianas/líquido cefalorraquidiano , Meningite Pneumocócica/líquido cefalorraquidiano , Neurônios/patologia , Streptococcus pneumoniae , Animais , Morte Celular , Linhagem Celular , L-Lactato Desidrogenase/metabolismo , Neurônios/efeitos dos fármacos , Coelhos , Proteínas Recombinantes/farmacologia , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
We examined whether experimental pneumococcal meningitis induced the 72-kd heat shock protein (HSP72), a sensitive marker of neuronal stress in other models of central nervous system (CNS) injury. Brain injury was characterized by vasculitis, cerebritis, and abscess formation in the cortex of infected animals. The extent of these changes correlated with the size of the inoculum (P less than 0.003) and with pathophysiologic parameters of disease severity, i.e., cerebrospinal fluid (CSF) lactate (r = 0.61, P less than 0.0001) and CSF glucose concentrations (r = -0.55, P less than 0.0001). Despite the presence of numerous cortical regions having morphologic evidence of injury, HSP72 was not detected in most animals. When present, only rare neurons were HSP72 positive. Western blot analysis of brain samples confirmed the paucity of HSP72 induction. The lack of neuronal HSP72 expression in this model suggests that at least some of the events leading to neuronal injury in meningitis are unique, when compared with CNS diseases associated with HSP72 induction.
Assuntos
Doenças do Sistema Nervoso Central/etiologia , Doenças do Sistema Nervoso Central/patologia , Proteínas de Choque Térmico/metabolismo , Meningite Pneumocócica/complicações , Meningite Pneumocócica/patologia , Animais , Western Blotting , Doenças do Sistema Nervoso Central/metabolismo , Glucose/líquido cefalorraquidiano , Lactatos/líquido cefalorraquidiano , Masculino , Meningite Pneumocócica/metabolismo , Ratos , Ratos EndogâmicosRESUMO
We evaluated the pharmacokinetics and therapeutic efficacy of ampicillin combined with sulbactam in a rabbit model of meningitis due to a beta-lactamase-producing strain of Escherichia coli K-1. Ceftriaxone was used as a comparison drug. The MIC and MBC were 32 and greater than 64 micrograms/ml (ampicillin), greater than 256 and greater than 256 micrograms/ml (sulbactam), 2.0 and 4.0 micrograms/ml (ampicillin-sulbactam [2:1 ratio, ampicillin concentration]) and 0.125 and 0.25 micrograms/ml (ceftriaxone). All antibiotics were given by intravenous bolus injection in a number of dosing regimens. Ampicillin and sulbactam achieved high concentrations in cerebrospinal fluid (CSF) with higher dose regimens, but only moderate bactericidal activity compared with that of ceftriaxone was obtained. CSF bacterial titers were reduced by 0.6 +/- 0.3 log10 CFU/ml/h with the highest ampicillin-sulbactam dose used (500 and 500 mg/kg of body weight, two doses). This was similar to the bactericidal activity achieved by low-dose ceftriaxone (10 mg/kg), while a higher ceftriaxone dose (100 mg/kg) produced a significant increase in bactericidal activity (1.1 +/- 0.4 log10 CFU/ml/h). It appears that ampicillin-sulbactam, despite favorable CSF pharmacokinetics in animals with meningitis, may be of limited value in the treatment of difficult-to-treat beta-lactamase-producing bacteria, against which the combination shows only moderate in vitro activity.
Assuntos
Ampicilina/uso terapêutico , Infecções por Escherichia coli/tratamento farmacológico , Meningites Bacterianas/tratamento farmacológico , Sulbactam/uso terapêutico , beta-Lactamases/biossíntese , Ampicilina/líquido cefalorraquidiano , Ampicilina/farmacocinética , Animais , Ceftriaxona/líquido cefalorraquidiano , Ceftriaxona/farmacocinética , Ceftriaxona/uso terapêutico , Quimioterapia Combinada/líquido cefalorraquidiano , Quimioterapia Combinada/farmacocinética , Quimioterapia Combinada/uso terapêutico , Infecções por Escherichia coli/microbiologia , Injeções Intravenosas , Meningites Bacterianas/líquido cefalorraquidiano , Testes de Sensibilidade Microbiana , Coelhos , Sulbactam/líquido cefalorraquidiano , Sulbactam/farmacocinéticaRESUMO
We evaluated the pharmacokinetics and therapeutic efficacy of piperacillin combined with tazobactam, a novel beta-lactamase inhibitor, in experimental meningitis due to a beta-lactamase-producing strain of K1-positive Escherichia coli. Different doses of piperacillin and tazobactam, as single agents and combined (8:1 ratio; dosage range, 40/5 to 200/25 mg/kg per h), and of ceftriaxone were given to experimentally infected rabbits by intravenous bolus injection followed by a 5-h constant infusion. The mean (+/- standard deviation) rates for penetration into the cerebrospinal fluid of infected animals after coadministration of both drugs were 16.6 +/- 8.4% for piperacillin and 32.5 +/- 12.6% for tazobactam. Compared with either agent alone, combination treatment resulted in significantly better bactericidal activity in the cerebrospinal fluid. The bactericidal activity of piperacillin-tazobactam was dose dependent: cerebrospinal fluid bacterial titers were reduced by 0.37 +/- 0.19 log10 CFU/ml per h with the lowest dose versus 0.96 +/- 0.25 log10 CFU/ml per h with the highest dose (P less than 0.001). At the relatively high doses of 160/20 and 200/25 mg of piperacillin-tazobactam per kg per h, the bactericidal activity of the combination was comparable to that of 10 and 25 mg of ceftriaxone per kg per h, respectively.
Assuntos
Antibacterianos/uso terapêutico , Infecções por Escherichia coli/tratamento farmacológico , Escherichia coli/enzimologia , Meningite/tratamento farmacológico , Ácido Penicilânico/uso terapêutico , Piperacilina/uso terapêutico , Animais , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/microbiologia , Testes de Sensibilidade Microbiana , Ácido Penicilânico/administração & dosagem , Ácido Penicilânico/farmacocinética , Piperacilina/administração & dosagem , Coelhos , Tazobactam , Inibidores de beta-LactamasesRESUMO
The present study was designed to determine whether cerebrovascular autoregulation is intact in experimental meningitis and to examine the relationship between fluctuations in cerebral blood flow (CBF) and increased intracranial pressure (ICP). Measurements of CBF were determined by the radionuclide microsphere technique in rabbits with experimental Streptococcus pneumoniae meningitis with simultaneous ICP monitoring via an implanted epidural catheter. CBF and ICP measurements were determined at baseline and when mean arterial blood pressure (MABP) was artificially manipulated by either pharmacologic or mechanical means. CBF was pressure passive with MABP through a range of 30-120 torr, and ICP directly correlated with CBF. These findings indicate that autoregulation of the cerebral circulation is lost during bacterial meningitis, resulting in a critical dependency of cerebral perfusion on systemic blood pressure, and that the parallel changes in ICP and in CBF suggest that fluctuations in CBF may influence intracranial hypertension in this disease.
Assuntos
Circulação Cerebrovascular , Homeostase , Meningite/fisiopatologia , Animais , Pressão Sanguínea , Dióxido de Carbono/sangue , Pressão Intracraniana , Meningite/terapia , Coelhos , Infecções Estreptocócicas/fisiopatologiaRESUMO
FCE 22101 is a new penem antibiotic with a spectrum of activity suggesting a possible role in the empirical treatment of meningitis. It appears to achieve a mean reduction in bacterial titre in CSF comparable with currently accepted agents for both pneumococcal and Escherichia coli meningitis. Its efficacy may, however, be variable. It does not achieve CSF level/MIC ratios as favourable as imipenem for the pathogens studied. Further studies are necessary to determine its role, if any, in this disease.
Assuntos
Antibacterianos/uso terapêutico , Carbapenêmicos , Infecções por Escherichia coli/tratamento farmacológico , Meningite Pneumocócica/tratamento farmacológico , Meningite/tratamento farmacológico , Animais , Antibacterianos/sangue , Atividade Bactericida do Sangue , Ceftriaxona/sangue , Ceftriaxona/uso terapêutico , Infecções por Escherichia coli/microbiologia , Imipenem/sangue , Imipenem/uso terapêutico , Meningite/microbiologia , Meningite Pneumocócica/microbiologia , Testes de Sensibilidade Microbiana , Penicilinas/sangue , Penicilinas/uso terapêutico , CoelhosAssuntos
Transtornos de Ansiedade/epidemiologia , Medo , Pânico , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova IorqueRESUMO
The present study discusses the development of dental health knowledge tests as part of an integrated dental health curriculum in the public school system of a rural community. It is part of a large project designed to test the effectiveness of a school-based dental health delivery system. Cognitive measures of dental health were designed to study the relationship of dental health knowledge to oral health behaviors. A review of the literature revealed no suitable dental health knowledge tests for grades K-6; new assessment measures were then developed by project staff. The tests consisted of 14 objectively scored tests--two parallel forms at each of the seven grade levels, K-6, and were administered four times to 1,942 students. Consistently, the tests have demonstrated high reliability estimates and low standard errors of measurement and indicate that the instruments are functioning as parallel forms and measuring the same dental concepts with equal precision.