RESUMO
Chemical probes are an indispensable tool for translating biological discoveries into new therapies, though are increasingly difficult to identify. Novel therapeutic targets are often hard-to-drug proteins, such as messengers or transcription factors. Computational strategies arise as a promising solution to expedite drug discovery for unconventional therapeutic targets. FRASE-bot exploits big data and machine learning (ML) to distill 3D information relevant to the target protein from thousands of protein-ligand complexes to seed it with ligand fragments. The seeded fragments can then inform either (i) de novo design of 3D ligand structures or (ii) ultra-large-scale virtual screening of commercially available compounds. Here, FRASE-bot was applied to identify ligands for Calcium and Integrin Binding protein 1 (CIB1), a promising but ligand-orphan drug target implicated in triple negative breast cancer. The signaling function of CIB1 relies on protein-protein interactions and its structure does not feature any natural ligand-binding pocket. FRASE-based virtual screening identified the first small-molecule CIB1 ligand (with binding confirmed in a TR-FRET assay) showing specific cell-killing activity in CIB1-dependent cancer cells, but not in CIB1-depleted cells.
RESUMO
BACKGROUND: Complex regional pain syndrome type I (CRPS-I), previously known as reflex sympathetic dystrophy, is common after conservatively or surgically treated wrist fractures. Several studies support the efficacy of vitamin C in preventing CRPS-I, although the data are somewhat conflicting. The primary objective of this systematic literature review and meta-analysis was to assess the efficacy of vitamin C therapy in preventing CRPS-I after a wrist fracture. METHODS: Randomised, placebo-controlled trials of vitamin C to prevent CRPS-I after wrist fractures were sought in the three main databases: PubMed (1980 to December 2015), CENTRAL (Central 2015, number 12), and Embase (1980 to December 2015). Two authors worked independently to select articles. Data from selected articles were collected independently. RESULTS: Three randomised placebo-controlled trials in a total of 875 patients were included. Treatment was non-operative in 758/890 (85.1%) fractures and operative in 132 (14.9%) fractures. Vitamin C supplementation was started on the day of the injury and continued for 50 days. In the group given 500mg of vitamin C daily, the risk ratio for CRPS-I was 0.54 (95%CI, 0.33-0.91; P=0.02). Thus, the risk of developing CRPS-I was significantly decreased by prophylactic treatment with 500mg of vitamin C per day. The heterogeneity rate was 65% (non-significant). CONCLUSION: Daily supplementation with 500mg of vitamin C per day for 50 days decreases the 1-year risk of CRPS-I after wrist fracture. LEVEL OF EVIDENCE: II, systematic review of level I and II studies.
Assuntos
Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Síndromes da Dor Regional Complexa/etiologia , Síndromes da Dor Regional Complexa/prevenção & controle , Fraturas do Rádio/complicações , Fraturas da Ulna/complicações , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Traumatismos do Punho/complicaçõesRESUMO
While Parkinson's disease is the result of dopaminergic dysfunction of the nigrostriatal system, the clinical manifestations of Parkinson's disease are brought about by alterations in multiple neural components, including cortical areas. We examined how 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration affected extracellular cortical glutamate levels by comparing glutamate levels in normal and MPTP-lesioned nonhuman primates (Macaca mulatta). Extracellular glutamate levels were measured using glutamate microelectrode biosensors. Unilateral MPTP-administration rendered the animals with hemiparkinsonian symptoms, including dopaminergic deficiencies in the substantia nigra and the premotor and motor cortices, and with statistically significant decreases in basal glutamate levels in the primary motor cortex on the side ipsilateral to the MPTP-lesion. These results suggest that the functional changes of the glutamatergic system, especially in the motor cortex, in models of Parkinson's disease could provide important insights into the mechanisms of this disease.
Assuntos
Dopamina/deficiência , Ácido Glutâmico/análise , Macaca mulatta/metabolismo , Córtex Motor/química , Transtornos Parkinsonianos/metabolismo , Substância Negra/química , Animais , Técnicas Biossensoriais , Contagem de Células , Neurônios Dopaminérgicos/enzimologia , Eletrodos Implantados , Feminino , Microeletrodos , Córtex Motor/patologia , Proteínas do Tecido Nervoso/análise , Substância Negra/patologia , Tirosina 3-Mono-Oxigenase/análiseRESUMO
BACKGROUND: Many women with breast cancer need psychological help to cope more effectively after treatment. Cognitive and behavioural techniques are not yet well established in France. A multi-site randomized study was conducted to evaluate the effects of a psycho-educational group intervention in this population. METHODS: Two hundred and three patients, recruited after primary treatment, were randomly assigned either to a treatment group (psycho-educational intervention) or to a waiting-list control group. The 8-week programme of 2 h sessions comprised of thematic discussions, information and training in stress management techniques. Evaluation at baseline, after 8 sessions, and 1 month after programme completion, included evaluations using the STAI, POMS, MAC, EORTC QLQ-C30 and EORTC QLQ-BR23 breast module scales. RESULTS: We observed a significant reduction in anxiety (STAI, POMS) among group participants, a reduction in anger, depression and fatigue (POMS), a significant improvement in vigor and interpersonal relationships (POMS), in emotional and role functioning, in health status and fatigue level (EORTC QLQ-C30). In contrast, coping strategies (MAC) were not significantly different between groups. No group-related negative effects were observed and the global satisfaction levels were very high. CONCLUSION: This study demonstrates the feasibility and effectiveness of a psycho-educational intervention, which can accelerate the reduction of those negative affects which are present at the end of treatment. It represents an excellent complement or an alternative to individual psycho-oncologic therapeutic support, widely proposed in France, and should now be tested in groups with other types of cancer and at other disease phases.
Assuntos
Neoplasias da Mama/psicologia , Neoplasias da Mama/terapia , Educação de Pacientes como Assunto/métodos , Psicoterapia de Grupo/métodos , Adaptação Psicológica , Adulto , Idoso , Ansiedade/diagnóstico , Ansiedade/psicologia , Ansiedade/terapia , Neoplasias da Mama/patologia , Depressão/diagnóstico , Depressão/psicologia , Depressão/terapia , Fadiga/psicologia , Estudos de Viabilidade , Feminino , França , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Inventário de Personalidade/estatística & dados numéricos , Psicometria , Qualidade de Vida/psicologia , Papel do Doente , Apoio Social , Resultado do TratamentoRESUMO
BACKGROUND: The use of hyperbaric oxygen for children with cerebral palsy has spread worldwide, despite little scientific evidence of efficacy. We did a randomised trial to assess the efficacy and side-effects of this form of therapy in children with cerebral palsy. METHODS: 111 children with cerebral palsy aged 3-12 years were randomly assigned hyperbaric oxygen (n=57) or slightly pressurised room air (n=54). All children received 40 treatments over 2 months. Hyperbaric oxygen treatment was 1 h in 100% oxygen at 1.75 atmospheres absolute (ATA); children on slightly pressurised air received air at 1.3 ATA (the lowest pressure at which pressure can be felt, thereby ensuring the maintenance of masking). The main outcome measure was gross motor function. Secondary outcomes included performance in activities of daily living, attention, working memory, and speech. FINDINGS: For all outcomes, both groups improved over the course of the study, but without any difference between the two treatments. The score on the global gross motor function measure increased by 3.0% in the children on slightly pressurised air and 2.9% in those on hyperbaric oxygen. The mean difference between treatments was -0.40 (95% CI -1.69 to 0.90, p=0.544). Other changes were seen in speech, attention, memory, and functional skills. Ear problems occurred in 27 children treated by hyperbaric oxygen and in 15 treated with hyperbaric air (p=0.004). INTERPRETATION: In this study, hyperbaric oxygen did not improve the condition of children with cerebral palsy compared with slightly pressurised air. The improvement seen in both groups for all dimensions tested deserves further consideration.
Assuntos
Paralisia Cerebral/terapia , Oxigenoterapia Hiperbárica/métodos , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Quebeque , Resultado do TratamentoRESUMO
AIM: The respective contribution of sex, type of nephropathy, degree of proteinuria, blood pressure, protein and sodium daily intakes, blood lipid profile, protidemia, hemoglobinemia, acidosis and CaPO4 product on the rate of renal failure progression is debated. PATIENTS AND METHODS: The link between these parameters and the decrease of creatinine clearance, deltaCcr (according to Cockroft) was assessed in uni- and multivariate analysis in a population of 49 patients (26 women; age 60+/-15 years, weight 79+/-15 kg) selected out of 173 presently treated hemodialysis patients on the basis of availability of a quarterly follow-up for 2 years before starting dialysis. The patients were advised a moderate protein and salt restriction which could be retrospectively assessed (on urinary excretion of urea and sodium) at, respectively, 0.82 g/kg/day and 6.5 g/day. RESULTS: The 2-year deltaCcr was 14+/-14 ml/min. It was not different in men and women. This decrease in Ccr was neither significantly different in gomerular disease (17+/-8, n = 14), diabetic nephropathy (12+/-6, n = 7), nephroangiosclerosis (15+/-8, n = 5), interstitial nephritis (12+/-10, n = 14), and PKD (11 +/-12, n = 9). Patients with antihypertensive drugs (n = 42) had a faster progression than those without drugs (n = 7): deltaCcr = 15+/-14 vs 7+/-7 ml/min (p < 0.05) in spite of comparable blood pressure but with higher proteinuria. Linear regression of deltaCcr with the initial and 2-year averaged values of the quantitative parameters showed a significant positive link for both values with cholesterol, hemoglobine and proteinuria and a negative one with protidemia. A positive link was observed with the initial value of bicarbonate and the 2-year mean of diastolic and mean blood pressures. No link at all was observed with urea and Na excretion, CaPO4 product and triglycerides. Multiple regression disclosed a significant link only for protidemia (negative with both initial and 2-year averaged value), diastolic BP (only for the 2-year averaged value and hemoglobinemia (for the initial value). When the patients were classified according to a threshold value of their protidemia, DBP, hemoglobinemia, and cholesterolemia those with the combination of 2 risk factors of progression (protidemia > or = 66 g/l, DBP > or = 90 mmHg, hemoglobinemia > 11 g/dl, proteinuria > or = 3 g/d, CT > 5 mmol/l) had a significantly greater decrease of Ccr than those with the 3 other combinations at the exception of the association of low protidemia with DBP. CONCLUSION: Diastolic hypertension and low protidemia are the 2 most important factors predicting progression of renal failure. A predictive synergy was furthermore pointed out between low protidemia or diastolic hypertension with proteinuria and cholesterol. On the contrary anemia attenuates progression linked to low protidemia, diastolic hypertension, proteinuria and high cholesterol.
Assuntos
Falência Renal Crônica/fisiopatologia , Diálise Renal , Anemia/complicações , Bicarbonatos/sangue , Proteínas Sanguíneas/análise , Cálcio/sangue , Colesterol/sangue , Creatinina/urina , Nefropatias Diabéticas/complicações , Progressão da Doença , Feminino , Glomerulonefrite/complicações , Humanos , Hipertensão/complicações , Lipídeos/sangue , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Análise Multivariada , Nefrite Intersticial/complicações , Nefroesclerose/complicações , Fósforo/sangue , Rim Policístico Autossômico Dominante/complicações , Proteinúria/complicações , Fatores de Risco , Sódio na Dieta/administração & dosagemRESUMO
The purpose was to examine the acute effects of a hyperbaric oxygen (HBO2) treatment on a) recovery following prolonged exercise and b) aerobic performance in a trained population. Subjects were six male and six female, trained runners with mean Vo2max values of 64.6 +/- 5.6 and 51.9 +/- 6.6 ml x kg(-1) x min(-1), respectively. Subjects performed four exercise-HBO2 conditions in random order: a) control, b) exercise-no HBO2, c) no exercise-HBO2; and d) exercise-HBO2. Exercise was a 90-min run at 75-80% of Vo2max x HBO2 treatments consisted of breathing 95% O2 at 2.5 atm abs for 90 min. At the end of each condition, aerobic performance was assessed with a VO2max test and by the oxygen cost of running on a treadmill at three submaximal velocities. Recovery was not enhanced following a single HBO2 treatment at 2.5 atm abs for 90 min, nor did it alter submaximal or maximal running performance.
Assuntos
Oxigenoterapia Hiperbárica , Consumo de Oxigênio , Resistência Física/fisiologia , Corrida/fisiologia , Adulto , Análise de Variância , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Oxigênio/sangue , Fatores Sexuais , Fatores de TempoRESUMO
Prostaglandin G/H synthase (PGHS) has been shown to generate peroxides to a significant extent in the retina and absorbs light at the lower end of the visible spectrum. We postulated that PGHS could be an important initial source of peroxidation in the retina exposed to light, which would in turn alter retinal function. Exposure of pig eyes (in vivo) to light (350 fc/3770 lx) caused after 3 h a 50% increase and by 5 h a 30% decrease in a- and b-wave amplitudes of the electroretinogram (ERG) which were comparable at 380-650 nm and 380-440 nm but were not observed at wavelengths > 450 nm. These effects of light were prevented by free radical scavengers (dimethylthiourea and high-dose allopurinol) and PGHS inhibitors (naproxen and diclofenac), but stable analogs of prostaglandins did not affect the ERG. Both increases and subsequent decreases in ERG wave amplitudes following light exposure in vivo were associated with increases in retinal prostaglandin and malondialdehyde (peroxidation product) levels, which were inhibited by the nonselective PGHS blockers, naproxen and diclofenac. Similar observations were made in vitro on isolated porcine eyecups as well as on retinal membranes exposed to light (250 fc/ 2700 lx) 380-650 nm and 380-440 nm but not at > 500 nm. Both PGHS-1 and PGHS-2 contributed equivalently to light-induced prostaglandin synthesis, as shown after selective PGHS-2 blockers, but mRNA expression of PGHS-1 and 2 was not affected by light. Finally, light stimulated activities of pure PGHS-1 and PGHS-2 isozymes, and these were also shown to produce superoxide radical (detected with fluorogenic spin trap, proxyl fluorescamine). Taken together, data suggest that PGHS- (1 and 2) is activated by short wavelength visible light, and in the retina is an important source of reactive oxygen species which in turn alter retinal electrophysiological function. PGHS thus seems a likely chromophore in setting forth photic-induced retinal injury. Findings provide an explanation for increased sensitivity of the retina to visible light predominantly at the far blue range of its spectrum.
Assuntos
Luz/efeitos adversos , Peróxidos/metabolismo , Prostaglandina-Endoperóxido Sintases/efeitos da radiação , Retina/enzimologia , Retina/efeitos da radiação , Animais , Eletrorretinografia/efeitos da radiação , Ativação Enzimática/efeitos da radiação , Estabilidade Enzimática/efeitos da radiação , Isoenzimas/genética , Isoenzimas/metabolismo , Isoenzimas/efeitos da radiação , Peroxidação de Lipídeos/efeitos da radiação , Malondialdeído/metabolismo , Malondialdeído/efeitos da radiação , Membranas/enzimologia , Membranas/efeitos da radiação , Peróxidos/efeitos adversos , Prostaglandina-Endoperóxido Sintases/genética , Prostaglandina-Endoperóxido Sintases/metabolismo , Prostaglandinas/metabolismo , Prostaglandinas/efeitos da radiação , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Mensageiro/efeitos da radiação , Retina/metabolismo , Superóxidos/metabolismo , Superóxidos/efeitos da radiação , SuínosRESUMO
To test the role of reactive oxygen species and cyclooxygenase products in the retinal hemodynamic changes induced by asphyxia, we measured retinal (RBF) and choroidal blood flows (ChBF), malondialdehyde (MDA), prostaglandin E2 (PGE2), 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), and thromboxane B2 (TxB2) in 1- to 3-day-old pigs treated with saline, the free radical scavengers U-74389F or high-dose allopurinol, the cyclooxygenase inhibitors ibuprofen or indomethacin, or the thromboxane synthase blocker CGS-13080 before and 5 and 60 min after a 5-min period of asphyxia. In saline-treated animals, RBF and ChBF increased 5 min after asphyxia and decreased at 60 min. The increases in RBF and ChBF at 5 min postasphyxia were slightly attenuated by cyclooxygenase blockers and free radical scavengers but not by thromboxane synthase inhibition, whereas all drugs prevented the decreases at 60 min. MDA, TxB2, PGE2, and 6-keto-PGF1 alpha increased 5 min after asphyxia; at 60 min, PGE2 and 6-keto-PGF1 alpha returned to nearly preasphyxial levels, but MDA and TxB2 continued to increase. Cyclooxygenase inhibition prevented the asphyxia-induced rise in MDA, and the free radical scavengers prevented that of prostanoids. In isolated eyecup preparations, H2O2 and cumene hydroperoxide constricted retinal arteries; this effect was blocked by cyclooxygenase and thromboxane synthase inhibitors. The data suggest that during oxidative stresses reactive oxygen species are generated from the cyclooxygenase pathway and, in turn, also activate the synthesis of thromboxane; the latter mediates the oxidative stress-induced ocular vasoconstriction that might trigger the neovascularization of retinopathy of prematurity.
Assuntos
Asfixia/metabolismo , Corioide/irrigação sanguínea , Peróxidos/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Retina/metabolismo , Vasos Retinianos/efeitos dos fármacos , 3,4-Metilenodioxianfetamina/farmacologia , Animais , Antioxidantes/farmacologia , Corioide/metabolismo , Dinoprostona/farmacologia , Sequestradores de Radicais Livres/farmacologia , Pregnatrienos/farmacologia , Prostaglandinas F/farmacologia , Espécies Reativas de Oxigênio/farmacologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Cloreto de Sódio/farmacologia , SuínosRESUMO
The use of 1 alpha-hydroxyvitamin D3 [1 alpha(OH)D3] derivatives in a uremic patient is justified only in the treatment of hyperparathyroidism (i.e. when plasma intact parathyroid hormone - PTH - levels are above five or three times the upper limit of normal according to whether the patient is on continuous ambulatory peritoneal dialysis or on hemodialysis and between 0.5-1.5, 1-2 and 2-3 times the upper limit of normal for a creatinine clearance of, respectively, 30, between 30 and 10, or below 10 ml/min/1.73 m2). The following prerequisites have however to be satisfied: (1) a good vitamin D3 repletion should be secured by plasma 25(OH(D) levels of 20-30 ng/ml (if necessary by administration of native vitamin D or 25(OH)D3), and (2) phosphate retention (which is aggravated by the increased phosphate intestinal absorption induced by the 1 alpha (OH)D derivatives) and the consequent possible hyperphosphatemia should be prevented or corrected by the oral administration of alkaline salts of calcium given before the meals as phosphate binders without inducing hypercalcemia. These prerequisites explain the narrow therapeutical margin of 1 alpha (OH)D3 derivatives in uremic patients before dialysis (more so in the adult than in the child) and the possible broadening of this margin in the patients on dialysis by the use of low dialysate calcium concentrations (1.25-1.00 mmol/l) in order to prevent hypercalcemia by inducing a negative perdialytic calcium balance. Once hyperphosphatemia is prevented by oral calcium, 1 alpha (OH)D3 derivatives have the advantage to suppress the transcription of the prepro PTH gene by a mechanism independent of an increase in plasma calcium. Controlled randomized trials have not confirmed the claimed advantage in efficacy and safety of the parenteral versus the oral route nor of the intermittent versus the daily mode of their administration. The advantages of using the so called 'nonhypercalcemic hyperphosphatemic' vitamin D3 derivatives in combination with oral calcium over 1 alpha(OH)D3 derivatives in the treatment of uremic hyperparathyroidism are still waiting for clinical demonstration. Vitamin D derivatives have no place in the treatment of aluminic bone diseases which necessitate long term deferoxamine treatment and prevention of aluminum exposure by the dialysate and the phosphate binders. They are not indicated in the treatment of 'idiopathic' adynamic bone disease which is due to uremia per se combined with an excessive PTH suppression for the degree of renal failure. This low bone turnover pattern is associated with an increased risk of hypercalcemia and hyperphosphatemia and necessitates only a stimulation of PTH secretion by inducing a negative calcium balance with a lower dialysate calcium concentration or simply by discontinuing the oral calcium supplement in the uremic patient not yet dialyzed. In rare cases this pattern is due to a granulomatosis and is corrected by prednisone.
Assuntos
Doenças Ósseas/complicações , Doenças Ósseas/tratamento farmacológico , Hidroxicolecalciferóis/uso terapêutico , Insuficiência Renal/complicações , Uremia/complicações , Adulto , Amiloidose/tratamento farmacológico , Animais , Criança , Humanos , Hiperparatireoidismo/complicações , Hiperparatireoidismo/tratamento farmacológico , Modelos Biológicos , Osteomalacia/tratamento farmacológico , Hormônio Paratireóideo/sangueRESUMO
PURPOSE: To study the role of free radicals in autoregulation of retinal blood flow (RBF) and choroidal blood flow (ChBF) and the contribution of the cyclooxygenase pathway in free radical formation during blood pressure changes in 1- to 3-day-old pigs. METHODS: Blood pressure was adjusted by inflating balloon-tipped catheters placed at the aortic isthmus and the aortic root to induce hypertension and hypotension, respectively. Blood flow was measured using the microsphere technique. Also, the effects of peroxides on retinal artery diameter were studied on eyecup preparations using time-frame photography processed by digital imaging. RESULTS: Blood gases and intraocular pressure (13 +/- 1 mm Hg) remained stable throughout the experiments. In control animals, RBF was constant only between 30 and 75 mm Hg of ocular perfusion pressure and ChBF increased as a function of ocular perfusion pressure (tau = 0.58, P < 0.01). Inhibition of peroxidation with the free radical scavenger 21-aminosteroid U74389F (2.5 mg/kg) widened the range of RBF and ChBF autoregulation (ocular perfusion pressure from 30 to 131 mm Hg). Hypertension caused an increase in the products of peroxidation, malondialdehyde, and hydroperoxides, as well as in prostaglandin E2, prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha in the retina and choroid of control animals; these changes were inhibited by the free radical scavengers U74389F (2.5 mg/kg) and high-dose allopurinol (140 mg/kg) as well as by the cyclooxygenase inhibitors ibuprofen (40 mg/kg) and indomethacin (5 mg/kg). In isolated eyecup preparations, H2O2 and cumene hydroperoxide dilated retinal vessels, and this effect was completely blocked by indomethacin. CONCLUSIONS: These findings indicate that free radicals play a major role in setting the upper limit of RBF and ChBF autoregulation of the newborn animal. In addition, there exists a positive feedback interaction between free radicals and cyclooxygenase activity in ocular tissues, such that during hypertension the cyclooxygenase pathway is an important producer of free radicals and in turn is also activated by them.
Assuntos
Corioide/irrigação sanguínea , Homeostase/fisiologia , Prostaglandinas/metabolismo , Vasos Retinianos/fisiologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Circulação Sanguínea/fisiologia , Radicais Livres/metabolismo , Hipertensão Ocular/fisiopatologia , Peróxidos/metabolismo , Pregnatrienos/farmacologia , Prostaglandina-Endoperóxido Sintases/metabolismo , Fluxo Sanguíneo Regional/fisiologia , Suínos , VasodilataçãoRESUMO
A comparative double blind trial was undertaken of the efficacy of cephradine, amoxycillin and phenoxymethylpenicillin in the treatment of acute dentoalveolar abscesses. Patients were admitted to the trial with acute dentoalveolar abscesses with systemic involvement and assessments were made of pain, swelling, temperature and lymphadenopathy. After admission to the trial appropriate surgical therapy was undertaken. The patients were then given either phenoxymethylpenicillin 250 mg four times daily, cephradine 500 mg twice daily or amoxycillin 250 mg three times daily, all for 5 days. The patients were assessed after 2 days and 5 days. All the patients recovered with those taking cephradine showing the best recovery in the first two days of treatment.
Assuntos
Amoxicilina/uso terapêutico , Cefradina/uso terapêutico , Penicilina V/uso terapêutico , Abscesso Periapical/tratamento farmacológico , Actinomyces/efeitos dos fármacos , Adolescente , Adulto , Idoso , Bacteroides/efeitos dos fármacos , Método Duplo-Cego , Feminino , Haemophilus influenzae/efeitos dos fármacos , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Medição da Dor , Abscesso Periapical/microbiologia , Streptococcus/efeitos dos fármacos , Veillonella/efeitos dos fármacosRESUMO
Plasma concentrations of bupivacaine were measured in patients after stellate ganglion block using either 10 or 20 ml of 0.25% plain solution. The mean peak concentrations were greater in the larger volume group, but this was not statistically significant. From 30 min after injection, there was a significantly greater plasma concentration in the larger volume group. The concentrations approached the limit of detection in the smaller volume group at 2 h after block.
Assuntos
Bloqueio Nervoso Autônomo , Bupivacaína/sangue , Gânglio Estrelado , Anestesia Local , Bupivacaína/administração & dosagem , Relação Dose-Resposta a Droga , Humanos , Injeções , Estudos Prospectivos , Fatores de TempoRESUMO
Old hemorrhagic lesions in the brain are characteristically surrounded by a band of hemosiderin-containing tissue. This region is typically of low signal intensity on long-echo-time (TE) radio-frequency (RF) spin-echo magnetic resonance (MR) images and on gradient-echo MR images. To determine the cause of signal loss in this band, the authors measured the signal that arises from imaging such a region with use of an RF spin-echo technique with a 180 degrees pulse incrementally displaced from TE/2. The incremental loss of signal was small. Using an agar phantom containing iron particles, the authors also showed that signal loss results primarily from diffusion in magnetic gradients. They conclude that most signal loss in the dark band surrounding areas of late-stage hemorrhage arises from diffusion in areas of magnetic inhomogeneity.
Assuntos
Hemorragia Cerebral/diagnóstico , Imageamento por Ressonância Magnética , Óxidos , Adulto , Ágar , Neoplasias Encefálicas/diagnóstico , Criança , Feminino , Óxido Ferroso-Férrico , Hemangioma Cavernoso/diagnóstico , Humanos , Aumento da Imagem , Ferro , Imageamento por Ressonância Magnética/métodos , Masculino , Óleo Mineral , Modelos Estruturais , Óleos de Plantas , Propilenoglicóis , ÁguaRESUMO
The authors measured polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) in maternal serum, cord blood, placenta, and serial samples of breast milk from 868 women. Almost all samples of breast milk showed detectable levels of both chemicals. Overall, values for DDE in this study are within the range of those found previously, whereas those for PCBs are somewhat higher. Possible causes of variation in levels were investigated. For DDE, older women, Black women, cigarette smokers, and women who consumed sport fish during pregnancy had higher levels; only age and race showed large effects. For PCBs, older women, women who regularly drink alcohol, and primiparae had higher levels. In addition, both chemicals showed modest variation across occupational groupings. Casual exposure to a PCB spill did not result in chemical levels different from background. In general, women have higher levels in their first lactation and in the earlier samples of a given lactation, and levels decline both with time spent breast-feeding and with number of children nursed. These striking declines are presumably a measure of exposure to the child.
Assuntos
Diclorodifenil Dicloroetileno/análise , Lactação , Leite Humano/análise , Bifenilos Policlorados/análise , Adolescente , Adulto , Negro ou Afro-Americano , Aleitamento Materno , Pré-Escolar , Colostro/análise , Diclorodifenil Dicloroetileno/sangue , Feminino , Sangue Fetal/análise , Contaminação de Alimentos , Humanos , Lactente , Recém-Nascido , Idade Materna , North Carolina , Placenta/análise , Bifenilos Policlorados/sangue , Gravidez , FumarAssuntos
Queimaduras/reabilitação , Hidroterapia , Águas Minerais , Cicatriz , Contratura/reabilitação , HumanosAssuntos
Balneologia , Queimaduras/complicações , Cicatriz/terapia , Águas Minerais , Humanos , MétodosRESUMO
Hardy, Paul H., Jr. (The Johns Hopkins University School of Medicine, Baltimore, Md.), and Carole O. Munro. Nutritional requirements of anaerobic spirochetes. I. Demonstration of isobutyrate and bicarbonate as growth factors for a strain of Treponema microdentium. J. Bacteriol. 91:27-32. 1966.-The previously reported ability of a microaerophilic diphtheroid to support the growth of some oral spirochetes resides in the acid-distillable fraction of the culture fluid. This fraction can be replaced by isobutyrate and, to a lesser extent, by 2-methylbutyrate. When media are supplemented with isobutyrate alone, there is a prolonged lag phase before spirochetal growth commences, but when sodium bicarbonate is also added the lag phase is shortened, and both the growth rate and the total yield are increased. Serum, in low concentration, also acts as a growth stimulant, but it is inhibitory when present at higher concentrations.