RESUMO
Diabetes mellitus (DM) is a metabolic disorder characterized by persistent hyperglycemia. This state may lead to an increase in oxidative stress, which contributes to the development of diabetes complications, including diabetic kidney disease. Potentilla indica is a traditional medicinal herb in Asia, employed in the treatment of several diseases, including DM. In this study, we investigated the antioxidant effect of the ethyl acetate extract of Potentilla indica both in vitro and on kidneys of streptozotocin-induced diabetic male rats. Firstly, phytochemicals were identified via UPLC-MS/MS, and their in vitro antioxidant capabilities were evaluated. Subsequently, male Wistar rats were assigned into four groups: normoglycemic control, diabetic control, normoglycemic treated with the extract, and diabetic treated with the extract. At the end of the treatment, fasting blood glucose (FBG) levels, creatinine, blood urea nitrogen (BUN), and uric acid were estimated. Furthermore, the kidneys were removed and utilized for the determination of mitochondrial reactive oxygen species (ROS) production, mitochondrial respiratory chain complex activities, mitochondrial lipid peroxidation, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities. The in vitro findings showed that the major phytochemicals present in the extract were phenolic compounds, which exhibited a potent antioxidant activity. Moreover, the administration of the P. indica extract reduced creatinine and BUN levels, ROS production, and lipid peroxidation and improved mitochondrial respiratory chain complex activity and GSH-Px, SODk, and CAT activities when compared to the diabetic control group. In conclusion, our data suggest that the ethyl acetate extract of Potentilla indica possesses renoprotective effects by reducing oxidative stress on the kidneys of streptozotocin-induced diabetic male rats.
RESUMO
BACKGROUND: Fetal alcohol spectrum disorder (FASD) is a lifelong condition. Early interventions targeting core neurocognitive deficits have the potential to confer long-term neurodevelopmental benefits. Time-targeted choline supplementation is one such intervention that has been shown to provide neurodevelopmental benefits that emerge with age during childhood. We present a long-term follow-up study evaluating the neurodevelopmental effects of early choline supplementation in children with FASD approximately 7 years on average after an initial efficacy trial. METHODS: The initial study was a randomized, double-blind, placebo-controlled trial of choline vs. placebo in 2.5 to 5 year olds with FASD. Participants in this long-term follow-up study include 18 children (9 placebo; 9 choline) seen 7 years on average following initial trial completion. The mean age at follow-up was 11.0 years old. Diagnoses were 28% fetal alcohol syndrome (FAS), 28% partial FAS, and 44% alcohol-related neurodevelopmental disorder. The follow-up included measures of executive functioning and an MRI scan. RESULTS: Children who received choline had better performance on several tasks of lower-order executive function (e.g., processing speed) and showed higher white matter microstructure organization (i.e., greater axon coherence) in the splenium of the corpus callosum compared to the placebo group. CONCLUSIONS: These preliminary findings, although exploratory at this stage, highlight potential long-term benefits of choline as a neurodevelopmental intervention for FASD and suggest that choline may affect white matter development, representing a potential target of choline in this population. TRIAL REGISTRATION: Prior to enrollment, this trial was registered with clinicaltrials.gov ( NCT01149538 ) on June 23, 2010.
Assuntos
Transtornos do Espectro Alcoólico Fetal , Substância Branca , Criança , Gravidez , Feminino , Humanos , Pré-Escolar , Transtornos do Espectro Alcoólico Fetal/tratamento farmacológico , Colina/uso terapêutico , Corpo Caloso/diagnóstico por imagem , Seguimentos , Substância Branca/diagnóstico por imagemRESUMO
Oxidative stress is a factor that contributes to the development of complications in diabetes; however, its effects can be counteracted using exogenous antioxidants that are found in some plants, which is why people turn to traditional medicines in the search for therapeutic treatment. Justicia spicigera has been demonstrated to have the capacity to reduce glycemic levels; however, its effects on non-insulin-dependent organs such as the liver have not been reported. During 30 days of administration of Justicia spicigera ethanol extract, the blood glucose and weight of rats were measured every 5 days. Once the treatment was concluded, the rats were sacrificed. Corporal weight, blood glucose, cholesterol, very-low-density lipoprotein (VLDL), triglycerides, total lipids, and liver profile were reduced in the diabetic condition and normalized with the application of ethanol extract from J. spicigera (EJS). Additionally, there was a significant increase in catalase and superoxide dismutase activity in the control diabetic rats, a decrease in their activity with the extract administration, and no effect on normoglycemic rats. In conclusion, EJS is considered to be capable of reducing oxidative stress by maintaining diminished lipid and liver function profiles in male Wistar rats with streptozotocin-induced diabetes.
Assuntos
Diabetes Mellitus Experimental , Justicia , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Glicemia , Diabetes Mellitus Experimental/tratamento farmacológico , Etanol/farmacologia , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Masculino , Estresse Oxidativo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , EstreptozocinaRESUMO
Abnormalities in lipid metabolism, associated with increased risk of cardiovascular disease (CVD), frequently occur in people with diabetes. Eryngium carlinae is a plant used in traditional medicine to treat lipid abnormalities. The chemical composition and hypolipidemic activity of the ethanolic extract of E. carlinae were analyzed to broaden our knowledge of its mechanism of action. The ethanolic extract of E. carlinae was tested for hypolipidemic activity by oral administration for 40 days. Atorvastatin, a widely used statin, was also administered to compare its effect with that of the extract. Serum was used for analysis of the lipid profile and liver microsomes to assess 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity and low-density lipoprotein receptor (LDL-r) levels. The extract was able to reduce total cholesterol and non-high-density lipoprotein cholesterol (C-HDL) levels and increase the C-HDL levels reduced in diabetes, decreasing the atherogenic index and therefore the risk of suffering CVD at the same level as atorvastatin. The HMG-CoA reductase activity and LDL-r levels were not modified by the administration of E. carlinae. The results demonstrate the hypolipidemic potential of ethanol extract of E. carlinae and support its use in traditional medicine as a hypolipidemic agent.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Eryngium/química , Hipolipemiantes/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Atorvastatina , Colesterol/sangue , Etanol , Hidroximetilglutaril-CoA Redutases/metabolismo , Lipídeos/sangue , Microssomos Hepáticos/enzimologia , Ratos , Ratos WistarRESUMO
Background: Postoperative urinary retention (PO-UR) is an acute and painful inability to void after surgery that can lead to complications and delayed hospital discharge. Standard treatment with a urinary catheter is associated with a risk of infection and can be distressing, undignified and uncomfortable. This systematic review aimed to identify effective interventions for the prevention and treatment of PO-UR that might be alternatives to urinary catheterization. Methods: Electronic databases were searched from inception to September 2017. Randomized trials of interventions for the prevention or treatment of PO-UR were eligible for inclusion. Studies were assessed for risk of bias using the Cochrane (2.0) tool. Two reviewers were involved at all review stages. Where possible, data were pooled using random-effects meta-analysis. The overall quality of the body of evidence was rated using the GRADE approach. Results: Some 48 studies involving 5644 participants were included. Most interventions were pharmacological strategies to prevent PO-UR. Based on GRADE, there was high-certainty evidence to support replacing morphine in a regional anaesthetic regimen, using alpha-blockers (number needed to treat to prevent one case of PO-UR (NNT) 5, 95 per cent c.i. 5 to 7), the antispasmodic drug drotaverine (NNT 9, 7 to 30) and early postoperative mobilization (NNT 5, 4 to 8) for prevention, and employing hot packs or gauze soaked in warm water for treatment (NNT 2, 2 to 4). Very few studies reported on secondary outcomes of pain, incidence of urinary tract infection or duration of hospital stay. Conclusion: Promising interventions exist for PO-UR, but they need to be evaluated in randomized trials investigating comparative clinical and cost effectiveness, and acceptability to patients.
Assuntos
Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/terapia , Retenção Urinária/terapia , Antagonistas Adrenérgicos alfa/uso terapêutico , Analgésicos Opioides/efeitos adversos , Anestesia/efeitos adversos , Anestesia/métodos , Deambulação Precoce , Humanos , Hipertermia Induzida/métodos , Morfina/efeitos adversos , Parassimpatolíticos/uso terapêutico , Complicações Pós-Operatórias/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Retenção Urinária/etiologiaRESUMO
The insulin superfamily, characterized by common disulphide bonds, includes not only insulin but also insulin-like peptides such as relaxin-1 and relaxin-3. The actions of relaxin-3 are largely unknown, but recent work suggests a role in regulation of food intake. Relaxin-3 mRNA is highly expressed in the nucleus incertus, which has extensive projections to the hypothalamus, and relaxin immunoreactivity is present in several hypothalamic nuclei. In the rat, relaxin-3 binds and activates both relaxin family peptide receptor 1, which also binds relaxin-1, and a previously orphaned G protein-coupled receptor, RXFP3. These receptors are extensively expressed in the hypothalamus. The aims of these studies were twofold: 1) map the hypothalamic site(s) of the orexigenic action of relaxin-3 and 2) examine the site(s) of neuronal activation following central relaxin-3 administration. After microinjection into hypothalamic sites, human relaxin-3 (H3; 180 pmol) significantly stimulated 0- to 1-h food intake in the supraoptic nucleus (SON), arcuate nucleus (ARC), and the anterior preoptic area (APOA) [SON 0.4+/-0.2 (vehicle) vs. 2.9+/-0.5 g (H3), P<0.001; ARC 0.7+/-0.3 (vehicle) vs. 2.7+/-0.2 g (H3), P<0.05; and APOA 0.8+/-0.1 (vehicle) vs. 2.2+/-0.2 g (H3), P<0.05]. Cumulative food intake was significantly increasedAssuntos
Mapeamento Encefálico
, Hipotálamo/efeitos dos fármacos
, Hipotálamo/fisiologia
, Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
, Proteínas do Tecido Nervoso/farmacologia
, Neuropeptídeos/metabolismo
, Proteínas Proto-Oncogênicas c-fos/metabolismo
, Relaxina/farmacologia
, Animais
, Ingestão de Alimentos/efeitos dos fármacos
, Imuno-Histoquímica
, Masculino
, Modelos Biológicos
, Orexinas
, Ratos
, Ratos Wistar
RESUMO
High-resolution analyses of a late Holocene core from Kettle Lake in North Dakota reveal coeval fluctuations in loss-on-ignition carbonate content, percentage of grass pollen, and charcoal flux. These oscillations are indicative of climate-fuel-fire cycles that have prevailed on the Northern Great Plains (NGP) for most of the late Holocene. High charcoal flux occurred during past moist intervals when grass cover was extensive and fuel loads were high, whereas reduced charcoal flux characterized the intervening droughts when grass cover, and hence fuel loads, decreased, illustrating that fire is not a universal feature of the NGP through time but oscillates with climate. Spectral and wavelet analyses reveal that the cycles have a periodicity of approximately = 160 yr, although secular trends in the cycles are difficult to identify for the entire Holocene because the periodicity in the early Holocene ranged between 80 and 160 yr. Although the cycles are evident for most of the last 4,500 yr, their occasional muting adds further to the overall climatic complexity of the plains. These findings clearly show that the continental interior of North America has experienced short-term climatic cycles accompanied by a marked landscape response for several millennia, regularly alternating between dual landscape modes. The documentation of cycles of similar duration at other sites in the NGP, western North America, and Greenland suggests some degree of regional coherence to climatic forcing. Accordingly, the effects of global warming from increasing greenhouse gases will be superimposed on this natural variability of drought.
Assuntos
Desastres , Incêndios , Poaceae , Carbonatos/análise , Clima , Ecossistema , Água Doce , América do Norte , Oscilometria , Periodicidade , Pólen/fisiologia , Solo , TempoRESUMO
Localized delivery could decrease the systemic side effects of toxic chemotherapy drugs. The unique delivery agents we examine consist of microbubbles with an outer lipid coating, an oil layer, and a perfluorobutane gas core. These structures are 0.5-12 microm in radius at rest. Oil layers of these acoustically active lipospheres (AALs) range from 0.3-1.5 microm in thickness and thus the agents can carry a large payload compared to nano-scale drug delivery systems. We show that triacetin-based drug-delivery vehicles can be fragmented using ultrasound. Compared with a lipid-shelled contrast agent, the expansion of the drug-delivery vehicle within the first cycle is similar, and a subharmonic component is demonstrated at an equivalent radius, frequency, and driving pressure. For the experimental conditions explored here, the pulse length required for destruction of the drug-delivery vehicle is significantly greater, with at least five cycles required, compared with one cycle for the contrast agent. For the drug-delivery vehicle, the observed destruction mechanism varies with the initial radius, with microbubbles smaller than resonance size undergoing a symmetric collapse and producing a set of small, equal-sized fragments. Between resonance size and twice resonance size, surface waves become visible, and the oscillations become asymmetrical. For agents larger than twice the resonance radius, the destruction mechanism changes to a pinch-off, with one fragment containing a large fraction of the original volume.
Assuntos
Meios de Contraste/química , Lipossomos/química , Nanotecnologia , Sonicação , Óleo de Soja/química , Triacetina/química , Sistemas de Liberação de Medicamentos , Microesferas , Tamanho da Partícula , Pressão , Sensibilidade e Especificidade , ViscosidadeRESUMO
PURPOSE: Transurethral resection of the prostate is the standard operation for acute urinary retention, although laser prostatectomy is reportedly effective and safe. The ClasP (conservative management, laser, transurethral resection of the prostate) study compared transurethral prostatic resection and noncontact neodymium (Nd):YAG visual laser assisted prostatectomy for treatment of acute urinary retention. MATERIALS AND METHODS: This study was a multicenter randomized controlled trial, analyses were by intention to treat and followup was at 7.5 months after randomization. Primary outcomes were treatment failure, and included International Prostate Symptom Score, International Prostate Symptom Score quality of life score, residual urine and flow rate. Secondary outcomes included complications, and duration of catheterization and hospitalization. RESULTS: A total of 148 men were randomized to transurethral prostatic resection (74) and laser (74). There were fewer treatment failures after prostatic resection (p = 0.008) and fewer men after resection required secondary surgery for poor results (1 versus 7, p = 0.029). Maximum flow rates after transurethral prostatic resection were better than after laser (mean difference 4.4 ml. per second). Comparison of symptom and quality of life scores demonstrated that any clinically significant advantage for laser could be ruled out. Patients stayed a mean of 2 extra days in the hospital after resection. The duration of catheterization was greater after laser but significantly fewer major treatment complications were found with laser therapy. CONCLUSIONS: Transurethral prostatic resection was more effective, resulted in fewer failures than laser treatment and remains the procedure of choice for men with acute urinary retention.
Assuntos
Terapia a Laser/métodos , Qualidade de Vida , Ressecção Transuretral da Próstata/métodos , Retenção Urinária/cirurgia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Intervalos de Confiança , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neodímio , Razão de Chances , Sensibilidade e Especificidade , Resultado do Tratamento , Retenção Urinária/diagnósticoRESUMO
PURPOSE: Transurethral prostatic resection is the gold standard surgical treatment in men with lower urinary tract symptoms suggestive of bladder outlet obstruction but it has also been related to some risks, such as a relatively high rate of blood transfusion, sexual function problems and so forth. Transurethral prostatic incision is a simpler and less invasive procedure than transurethral prostatic resection. However, it is underused. We systematically reviewed all published randomized controlled trials comparing the effectiveness of transurethral prostatic incision with standard transurethral prostatic resection for bladder outlet obstruction and performed a meta-analysis of the available relevant data. MATERIALS AND METHODS: Nine randomized controlled trials comparing the treatment effectiveness of transurethral prostatic resection and transurethral prostatic incision were identified, evaluated and reviewed in a meta-analysis. The quality of these studies was also appraised. RESULTS: Each treatment achieved clear improvements in subjective and objective outcomes. The improvement in symptoms was equivalent 12 months postoperatively for transurethral prostatic incision and resection. For maximum flow rate transurethral prostatic resection resulted in greater improvement than transurethral prostatic incision. However, transurethral prostatic incision had several advantages over transurethral prostatic resection, such as lower incidence of complications, fewer blood transfusions, decreased risk of retrograde ejaculation, and shorter operative time and hospital stay. Also, the treatments had an equivalent incidence of postoperative catheterization duration and reoperation rate within the first 12 months. Furthermore, patients in each group had a similar subjective view of the treatments received. CONCLUSIONS: In the first 12 months after surgery transurethral prostatic incision has effectiveness that is equivalent to transurethral prostatic resection for treating patients with suspected benign prostatic obstruction who have a relatively small prostate. However, there is little evidence on the relative long-term effectiveness of the 2 treatments 2 to 5 or 10 years after surgery. There is no clear cutoff point for prostate size that leads to good results after transurethral prostatic incision. A large-scale, multicenter randomized controlled trial is now required to evaluate comprehensively the effectiveness, impact on quality of life and overall cost of transurethral prostatic incision compared with transurethral prostatic resection.
Assuntos
Próstata/cirurgia , Ressecção Transuretral da Próstata , Obstrução do Colo da Bexiga Urinária/cirurgia , Humanos , Masculino , Complicações Pós-Operatórias , Ensaios Clínicos Controlados Aleatórios como Assunto , Ressecção Transuretral da Próstata/efeitos adversos , Uretra/cirurgiaRESUMO
Under controlled-environment conditions, ethametsulfuron-methyl doses that inhibited growth by 50% (ED(50)) were >100 and <1 g of active ingredient (ai) ha(-)(1) for ethametsulfuron-methyl-resistant (R) and -susceptible (S) wild mustard, respectively. There were no differences between the two biotypes with regard to absorption and translocation of the herbicide. Three days after treatment, approximately 90, 5, and 2% of the applied [(14)C]ethametsulfuron-methyl was found in the treated leaf, foliage, and roots of each biotype, respectively. Acetolactate synthase extracted from the two biotypes was equally sensitive to both ethametsulfuron-methyl and chlorsulfuron. These results indicate that resistance was not due to differences in the target site, absorption, or translocation. However, ethametsulfuron-methyl was metabolized more rapidly in the R than the S biotype. Approximately 82, 73, 42, 30, and 17% of the recovered radioactivity remained as ethametsulfuron-methyl in R wild mustard 3, 6, 18, 48, and 72 h after treatment, respectively. Conversely, 84, 79, 85, and 73% of the (14)C was ethametsulfuron-methyl in the S biotype 12, 24, 48, and 72 h after treatment, respectively. On the basis of these results, it is proposed that resistance is due to enhanced metabolism of ethametsulfuron-methyl in the R biotype.
Assuntos
Benzoatos/farmacologia , Herbicidas/farmacologia , Mostardeira/metabolismo , Plantas Medicinais , Triazinas/farmacologia , Absorção , Cromatografia Líquida de Alta Pressão , Resistência a Medicamentos , Mostardeira/efeitos dos fármacosRESUMO
PURPOSE: We assessed the effectiveness of laser therapy versus transurethral prostatic resection in men with symptomatic chronic urinary retention secondary to benign prostatic enlargement. MATERIALS AND METHODS: This trial was multicenter, pragmatic and randomized. Analysis was done by intent to treat. Laser therapy involved neodymium:YAG noncontact visual prostate ablation, while transurethral prostatic resection was performed by standard electroresection. Patients were included in our study if they reported moderate to severe lower urinary tract symptoms with an International Prostate Symptom Score (I-PSS) of 8 or more, benign prostatic enlargement and a persistent post-void residual urine volume of more than 300 ml. Followup was 7.5 months. Primary outcome measures included the I-PSS, I-PSS quality of life score, maximum urinary flow and post-void residual urine volume. Secondary outcome measures included treatment failure, complications, hospital stay and catheterization time. RESULTS: A total of 82 patients agreed to be randomized to receive laser therapy (38) or transurethral prostatic resection (44). There were significant improvements in all primary outcomes in each group from randomization to followup. Transurethral prostatic resection was significantly better than laser therapy for I-PSS and maximum urinary flow values (p = 0.035 and 0.029, respectively) but there were no differences in post-void residual urine volume and I-PSS quality of life score between the groups. We noted significantly more treatment failures with laser therapy than resection (8 versus 0, p = 0.0014), although only 3 patients required resection after laser therapy because of persistent symptoms. In addition, hospital stay after resection was 2-fold that after laser therapy (ratio of geometric means 2.01, 95% confidence interval 1.54 to 2.61, p <0.0001). However, time to catheter removal was 9 times longer in the laser therapy group (p <0. 0001). Complication rates were significantly higher for transurethral prostatic resection (chi-square 5.05, 1 df, p = 0.025). CONCLUSIONS: Transurethral prostatic resection is more effective than laser ablation in men with chronic urinary retention in terms of symptom score, maximum urinary flow and failure. However, men who underwent resection had significantly more treatment complications and were hospitalized longer than those who received laser therapy. This finding implies that laser ablation therapy may have a role in patients at higher risk who are willing to accept a lower level of effectiveness in exchange for decreased complication rates and hospital stay.
Assuntos
Terapia a Laser , Hiperplasia Prostática/cirurgia , Ressecção Transuretral da Próstata , Retenção Urinária/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Hiperplasia Prostática/complicações , Índice de Gravidade de Doença , Retenção Urinária/etiologiaRESUMO
PURPOSE: We evaluated the effectiveness of a new technology (noncontact laser therapy) versus that of standard surgery (transurethral prostatic resection) and conservative management for lower urinary tract symptoms associated with benign prostatic enlargement. MATERIALS AND METHODS: Men with uncomplicated lower urinary tract symptoms, that is no acute or chronic urinary retention, were randomized to receive laser therapy with a noncontact, side firing neodymium:YAG probe, standard transurethral prostatic resection or conservative management, including monitoring without active intervention, in a large multicenter pragmatic randomized controlled trial called the CLasP study. Primary outcomes were International Prostate Symptom Score (I-PSS), maximum urinary flow rate, a composite measure of success based on I-PSS and maximum urinary flow rate categories, I-PSS quality of life score and post-void residual urine volume. Secondary outcomes included treatment failure, hospital stay and major complications. Followup was 7.5 months after randomization. Intent to treat analysis was done using analysis of covariance, proportional odds models and the Newman-Keuls multiple comparisons procedure. RESULTS: Of symptomatic patients 117, 117 and 106 were randomized to receive laser therapy, transurethral prostatic resection and conservative management, respectively. Baseline characteristics were similar. All primary outcomes indicated that transurethral prostatic resection and laser therapy were superior to conservative management, and resection was superior to laser therapy. As measured by combined improved symptoms and maximum urinary flow, a successful outcome was achieved in 81%, 67% and 15% of men who underwent transurethral prostatic resection, laser therapy and conservative management, respectively. Hospital stay was significantly shorter and complications fewer for laser therapy than for resection but catheters were in place significantly longer. Men treated conservatively did not have deterioration or treatment failure. CONCLUSIONS: Laser therapy and transurethral prostatic resection are effective for decreasing lower urinary tract symptoms and post-void residual urine volume as well as improving quality of life and maximum urinary flow in the short term in men presenting with moderate to severe symptoms. Transurethral prostatic resection is superior to laser therapy in terms of effectiveness but some patients may elect laser therapy due to the shorter hospital stay and lower risk of complications. Conservative management may be acceptable and safe in men with lower urinary tract symptoms since we observed no marked deterioration in the short term.
Assuntos
Terapia a Laser , Hiperplasia Prostática/terapia , Ressecção Transuretral da Próstata , Idoso , Humanos , Masculino , Índice de Gravidade de DoençaRESUMO
PURPOSE: Inhibition of protein kinase C (PKC) activity has been demonstrated to reduce thermotolerance (TT), presumably by decreasing heat shock protein (HSP) production. Therefore, the interest was in evaluating this relationship further in two isogenic murine tumour cell lines: RIF-1 and its thermoresistant TR-4 selectant. MATERIALS AND METHODS: TT was induced in RIF-1 and TR-4 cells (45 degrees C for 15 min, then 37 degrees C for 6 h) with or without Ro31-8220, a specific inhibitor of PKC. PKC activity was assayed by determining the catalytic transfer of ATP to a specific substrate peptide. Survival was determined using the clonogenic assay. Apoptosis was quantitated by counting the number of cells demonstrating apoptosis after staining with acridine-orange/ ethidium bromide. Production of the inducible form of HSP70 was assessed using Western blot. RESULTS: At 2 microM Ro31-8220, >80% of PKC activity was inhibited in both cell lines, which was associated with no cytotoxicity at 37 degrees C. Basal HSP70 level was approximately 10-fold higher in the TR-4 compared with the RIF-1 cells. Upon TT induction, HSP70 level increased significantly in both cell lines, which was suppressed in the presence of Ro31-8220, but the relative amount of HSP70 remained high in the TR-4 cells. At 24 h, heat-induced apoptosis increased from 4 to 38% in RIF-1 cells in the presence of Ro31-8220, which was associated with a 26% reduction in clonogenic survival after thermotolerant heating. In contrast, <1% of TR-4 cells demonstrated apoptosis even with the highest dose of Ro31-8220, and no effect on survival was observed. CONCLUSION: Inhibition of PKC activity reduces HSP70 induction, which in turn is associated with promotion of heat-induced apoptosis in RIF-1 cells. However, the survival signals in the TR-4 cells are so strong, that even 80% inhibition of PKC activity has minimal impact on heat-induced apoptosis and survival in this thermoresistant cell line.
Assuntos
Apoptose/fisiologia , Temperatura Alta , Proteína Quinase C/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Inibidores Enzimáticos/farmacologia , Proteínas de Choque Térmico HSP70/biossíntese , Hipertermia Induzida , Indóis/farmacologia , Camundongos , Neoplasias Experimentais/enzimologia , Neoplasias Experimentais/terapia , Radiobiologia , Células Tumorais CultivadasRESUMO
PURPOSE: We examined data from multiple institutions to determine whether intravesical bladder stimulation therapy is effective in improving bladder compliance by increasing bladder capacity and lowering bladder storage pressures. MATERIALS AND METHODS: The charts of 568 patients from 11 institutions were evaluated. Of the 568 patients 335 had adequate and accurate pretreatment and posttreatment urodynamic studies, and were included in this study. A total of 155 patients was from Children's Memorial Hospital, while the remaining 180 were from 10 other institutions. Bladder capacity and bladder capacity pressure were determined for each patient before and after therapy. RESULTS: Overall, 53% of patients had increased bladder capacity of 20% or greater after treatment (average increase 105 cc), which represents a 63% increase from pretreatment values. This increase occurred in an average of 1.9 years. Further analysis of this subset of patients revealed that in 90% intravesical storage pressures were decreased or maintained within a safe range (less than 40 cm. water). Evaluation of patients who did not respond to bladder stimulation with a 20% or greater increase in bladder capacity revealed that they had nearly normal bladder capacity before therapy. When the data on bladder capacity and bladder capacity pressure from Children's Memorial Hospital were compared to results from the 10 other institutions, there were no appreciable differences. CONCLUSIONS: Bladder stimulation is effective in increasing bladder capacity without significantly elevating storage pressure in a majority of patients. We conclude that this technique is safe and effective in improving bladder compliance, and that it is reproducible elsewhere.
Assuntos
Terapia por Estimulação Elétrica , Bexiga Urinaria Neurogênica/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Bexiga Urinaria Neurogênica/fisiopatologiaRESUMO
BACKGROUND: Immunotherapy is a recognized component in the management of allergic rhinitis. Its efficacy has been evaluated in a number of clinical field trials. These methods of evaluation are limited by control of antigen exposure. OBJECTIVE: A study was designed to evaluate the efficacy of immunotherapy in ragweed-induced rhinoconjunctivitis using an environmental exposure unit. METHODS: Forty-three subjects were grouped into (1) immunotherapy group: ragweed-allergic subjects on maintenance ragweed immunotherapy for at least 2 years (N = 16), (2) positive control group: ragweed-allergic subjects who had never received immunotherapy (n = 16), and (3) negative control group: ragweed-nonallergic subjects (N = 11). Ragweed specific skin tests and ragweed IgE levels were obtained prior to exposure. The study was done in a room where levels of 2,500 to 3,000 grains m3 of ragweed were maintained over three hours. Symptoms were recorded every 15 minutes. RESULTS: Nasal symptoms in the immunotherapy group were significantly less than in the positive control group after 45 minutes (P = .025). Significant differences were not observed for ocular symptoms. Combined nasal and ocular scores were 50% less in the immunotherapy group than in the positive control group by 75 minutes (P = .039). Ragweed-specific skin tests and IgE were significantly less in the immunotherapy group than in the positive control group. Rhinoconjunctivitis symptoms in the negative control group were absent throughout. CONCLUSIONS: Controlled ragweed pollen exposure in this setting demonstrated that ragweed immunotherapy significantly reduced symptoms of ragweed-allergic rhinitis but had no significant effect on ocular symptoms. This system presents opportunities for additional studies on immunotherapy for allergic respiratory conditions.
Assuntos
Alérgenos/administração & dosagem , Alérgenos/uso terapêutico , Ambiente Controlado , Imunoterapia Ativa , Proteínas de Plantas/administração & dosagem , Proteínas de Plantas/uso terapêutico , Pólen/imunologia , Rinite Alérgica Sazonal/terapia , Adolescente , Adulto , Idoso , Alérgenos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Plantas/efeitos adversos , Rinite Alérgica Sazonal/imunologiaRESUMO
BACKGROUND/AIMS: Despite putative roles of calcium in biliary physiology and gallstone formation, quantitative aspects of calcium binding to bile salt (BS) monomers, simple micelles, mixed micelles, and vesicles, which constitute the lipid aggregates in bile, remain unexplored. METHODS: Calcium activity was measured using the calcium electrode in pathophysiologically relevant model biles composed of either individual BS species or a physiological mixture of glycine and taurine conjugates, as functions of lecithin and cholesterol contents and total lipid concentration. RESULTS: Calcium binding increased with increasing BS concentrations and lecithin contents and varied with species (dihydroxy > trihydroxy BS) and with conjugation (unconjugated > glycine conjugates > taurine conjugates). Although lecithin/cholesterol vesicles did not bind detectable calcium, when taurocholate was incorporated into membrane bilayers, calcium binding was substantially greater than with equimolar BS alone. Added cholesterol did not alter calcium binding, despite cholesterol saturation of biliary lipid aggregates and induction of liquid crystalline and solid crystalline-phase transitions. CONCLUSIONS: In model biles, most calcium is bound to mixed micelles, with minor contributions by BS monomers, simple micelles, and vesicles. It is proposed that BS-induced binding of calcium to vesicles and mixed micelles may be important in nucleation of cholesterol and bilirubinates from native bile.
Assuntos
Ácidos e Sais Biliares/fisiologia , Bile/metabolismo , Cálcio/metabolismo , Metabolismo dos Lipídeos , Fosfatidilcolinas/farmacologia , Ligação Competitiva , Colesterol/metabolismo , Gema de Ovo/metabolismo , Micelas , Fosfatidilcolinas/metabolismo , Ácido Taurocólico/metabolismoRESUMO
As family-centered care gradually became the norm in care of infants and children, relationships between staff, patients, and families became more complex. Because the complexity of these relationships was rarely, if ever, addressed, widely divergent, sometimes detrimental, behaviors evolved. Therapeutic relationships, which promote caring and define relationships with patients and families, are a positive and professional means to promote a family's control over their own child's health. This article describes assessment of nurse/patient/family relationships using family systems theory as a framework. The experience of implementing a culture shift toward therapeutic relationships is described.