RESUMO
AIM: Cerebral oxygenation (rSO2) is not routinely measured during pediatric cardiopulmonary resuscitation (CPR). We aimed to determine whether higher intra-arrest rSO2 was associated with return of spontaneous circulation (ROSC) and survival to hospital discharge. METHODS: Prospective, single-center observational study of cerebral oximetry using near-infrared spectroscopy (NIRS) during pediatric cardiac arrest from 2016 to 2020. Eligible patients had ≥30 s of rSO2 data recorded during CPR. We compared median rSO2 and percentage of rSO2 measurements above a priori thresholds for the entire event and the final five minutes of the CPR event between patients with and without ROSC and survival to discharge. RESULTS: Twenty-one patients with 23 CPR events were analyzed. ROSC was achieved in 17/23 (73.9%) events and five/21 (23.8%) patients survived to discharge. The median rSO2 was higher for events with ROSC vs. no ROSC for the overall event (62% [56%, 70%] vs. 45% [35%, 51%], p = 0.025) and for the final 5 minutes of the event (66% [55%, 72%] vs. 43% [35%, 44%], p = 0.01). Patients with ROSC had a higher percentage of measurements above 50% during the final five minutes of CPR (100% [100%, 100%] vs. 0% [0%, 29%], p = 0.01). There was no association between rSO2 and survival to discharge. CONCLUSIONS: Higher cerebral rSO2 during CPR for pediatric cardiac arrest was associated with higher rates of ROSC but not with survival to discharge.
Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca , Parada Cardíaca Extra-Hospitalar , Reanimação Cardiopulmonar/métodos , Circulação Cerebrovascular , Criança , Parada Cardíaca/terapia , Humanos , Parada Cardíaca Extra-Hospitalar/terapia , Oximetria/métodos , Estudos Prospectivos , Espectroscopia de Luz Próxima ao InfravermelhoRESUMO
Compression therapy plays a pivotal role in the treatment of venous leg ulcers and clinical observations include lymph stasis as contributing to the maintenance of chronic wounds. This finding raises the question whether further improvement in lymph circulation with manual lymph drainage (MLD) as a part of complex decongestive physiotherapy (CDP) can improve ulcer healing. We examined whether CDP improves healing of venous leg ulcers and compared the efficacy of CDP with that of multilayered compression with short-stretch bandages. Eight patients (mean age: 64.8 years, mean ulcer area: 23.07 cm2, duration of ulcers: 25.37 months) were treated with a 5-day-course of CDP and 9 patients (mean age: 70.77 years, mean ulcer area: 21.47 cm2, duration of ulcers: 15.8 months) were included in a 10-day-course of CDP. Control goup consisted of 9 patients (mean age: 56.33 years, mean ulcer area: 13.87 cm2, duration of ulcers: 6.11 months) receiving multilayered compression. Wound surface measurement was carried out on days 5 and 10 and ulcer area reduction rate was calculated as area (initial)-area (final)/time unit. There was no statistical difference between the 5-daycourse of CDP and compression of the same duration regarding ulcer healing (t=-1.62, df=15, p= 0.125). A 10-day-course of CDP significantly increased ulcer healing compared to compression of the same duration (t=-2.42, df=16, p= 0.039). Our preliminary results suggest that MLD as a part of CDP supports healing of venous leg ulcers.
Assuntos
Bandagens Compressivas , Drenagem Linfática Manual/métodos , Úlcera Varicosa/terapia , Cicatrização , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Estudos ProspectivosRESUMO
We employed surface probe-localized 31P-NMR spectroscopy to examine in situ the impact of short-term emergence (hypoxia) and resubmergence on phosphate metabolites and intracellular pH (pHi) in intact mussels. The use of intact organisms ensured that all intrinsic responses remained active while monitoring of individuals minimized uncertainties resulting from stochastic behavior and other individual differences. The use of a photoetched, balanced-match foil probe combined with 1H-NMR images allowed 31P-NMR spectra to be acquired from the posterior adductor muscle with good signal-to-noise. Upon emergence, all mussels exhibited an increase in [Pi], a decline in [phosphoarginine] and pHi, and very little changes in [ATP] with time. The complementary behavior of [phosphoarginine] and [Pi] indicated a precursor-product relationship involved in the maintenance of [ATP] but the similarity between [phosphoarginine] and pHi time-courses cannot be so readily explained. Irregularity in the time-courses of some parameters could have reflected stochastic gaping activity. Resubmergence responses exhibited a reversal of the emergence responses, except that the pHi eventually became supraalkaline with irregular fluctuations. This might be related to the 'oxygen debt' phenomenon and increased oxidative phosphorylation.
Assuntos
Bivalves/metabolismo , Fosfatos/metabolismo , Adaptação Fisiológica , Animais , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética/métodosRESUMO
Acetylation of hemoglobin by aspirin and other acetylating agents has been used to generate hemoglobin analogs with altered structural and functional properties, and may prove useful in the treatment of sickle cell disease. We have studied the acetylation of human hemoglobin using [1'-(13)C]acetylsalicylic acid in combination with two-dimensional HMQC and HSQC NMR analysis. The spectra of the acetylated hemoglobin exhibit a number of well resolved resonances. Several spectral assignment strategies were used: blocking the 2, 3-DPG binding site non-covalently with inositol hexaphosphate or covalently with a cross-linking agent, selective carbamylation of the N-terminal valine amino groups with cyanate, spin-labeling the hemoglobin at betaCys93, and analysis of a hemoglobin triple mutant: betaV1MH2DeltaK144R, in which betaLys144 is replaced by an arginine residue. These studies support the conclusion that the most rapidly acetylated residue is betaLys82 rather than betaLys144, as previously reported. Further, it is apparent that acetyl betaLys82 can give rise to several resonances due to additional acetylation of betaLys82' or other nearby residues. An additional assignment strategy involving comparison of the chemical shifts of the acetyl resonances observed for adducts of diamagnetic carbonmonoxyhemoglobin with the shifts observed in paramagnetic cyanomethemoglobin provides information about the location of the acetyl derivatives relative to the heme irons. This approach is limited, however, by the lack of well defined structural information for the lysine residues on the protein surface. Additional tentative assignments have also been made, using the above approaches.
Assuntos
Aspirina/química , Hemoglobinas/química , 2,3-Difosfoglicerato/química , Aspirina/análogos & derivados , Aspirina/síntese química , Sítios de Ligação , Isótopos de Carbono , Hemoglobinas/isolamento & purificação , Humanos , Espectroscopia de Ressonância Magnética , Metemoglobina/análogos & derivados , Metemoglobina/química , Mutação , Ácido Fítico/química , Marcadores de SpinRESUMO
Part one of this article describes the development of the nurse practitioner role in the UK. Part two reports on a research study examining whether or not community nurse practitioners were able to achieve a 'higher level of practice' as envisaged by the United Kingdom Central Council and will be published in next week's Nursing Standard.
Assuntos
Enfermagem em Saúde Comunitária/organização & administração , Profissionais de Enfermagem , Humanos , Papel do Profissional de Enfermagem , Desenvolvimento de Programas , Reino UnidoRESUMO
AIM: To establish whether or not community nurse practitioners were able to achieve a 'higher level of practice', as articulated by the United Kingdom Central Council. METHOD: Grounded theory was used as a framework for the research. Data were gathered using primary observation with some participation, and by interviewing community nurse practitioners and clinical managers. FINDINGS: 'Negotiation for autonomy' is the core category at the centre of the overall theoretical framework that emerged from the research data. Those working at a higher level of practice had the ability to negotiate for autonomy with GPs and other doctors. This ability gave them the opportunity to practise with the autonomy required to hold consultations, as first point of access, with patients with undifferentiated diagnoses, providing care through to discharge or referral to others. CONCLUSION: The research highlights that unless community nurse practitioners can negotiate their role with GPs and hospital doctors, they are unable to achieve a 'higher level of practice'.
Assuntos
Enfermagem em Saúde Comunitária/normas , Profissionais de Enfermagem/normas , Ética em Enfermagem , Humanos , Modelos de Enfermagem , Autonomia Profissional , Reino UnidoRESUMO
In a survey of double-bind design, 3 groups of approximately 70 student volunteers took 1 g L-ascorbic acid, 1 g D-isoascorbic acid, or placebo tablets every day for 15 weeks and the incidence and duration of colds were recorded. The group taking D-isoascrobic acid suffered 34% fewer colds than the other two groups; the results were also analyzed in relation to the sex and smoking habits of the volunteers. The rationale for investigating D-isoascorbic acid, an isomer of L-ascorbic acid which has limited antiscorbutic activity, is discussed.
Assuntos
Ácido Ascórbico/análogos & derivados , Ácido Ascórbico/uso terapêutico , Resfriado Comum/tratamento farmacológico , Ensaios Clínicos como Assunto , Resfriado Comum/prevenção & controle , Feminino , Humanos , Isomerismo , Masculino , Placebos , Fatores Sexuais , Fumar , Relação Estrutura-AtividadeRESUMO
The acetylation of ubiquitin by [acetyl-1-13C]aspirin has been studied using 2D NMR methods. Studies performed in a 50:50 H2O:D2O medium show doubling of the acetyl carbonyl resonances, indicating that all of the stable adducts formed involved amide linkages. Assignment of the heteronuclear multiple quantum coherence (HMQC) resonances was accomplished based on comparison of resonance intensities with the results of an Edman degradation analysis, pH titration studies of acetylated ubiquitin, and analysis of two ubiquitin mutants, K33R and K63R. The presence of a single tyrosine residue in close proximity to lysine-48 suggested another assignment strategy. Nitration of tyrosine-59 resulted in a small, pH-dependent shift of the resonance assigned to lysine-48, with a pK of 7.0, close to that expected for the nitrotyrosyl hydroxyl group. An additional adduct resonance with very low intensity also was observed and tentatively assigned to the acetylated N-terminal methionine residue. The relative rates of acetylation of the various lysine residues were obtained from time-dependent HMQC studies. Since no sample preparation artifacts were introduced, the levels of modification of the various residues could be determined with relatively high accuracy. Based on the time-dependent intensity data, the relative rate constants for modification of K6, K48, K63, K11, K33, and M1 were 1.0, 0.59, 0.43, 0.26, 0.23, and 0.03, respectively. These results were in much better agreement with amino accessibility predictions based on the crystal structure of the ubiquitin monomer than with predictions based on the ubiquitin structure in the crystallized dimeric and tetrameric forms. This approach provides a useful basis for understanding how local environmental factors can influence protein adduct formation, as well as for comparing the extent and specificity of various acetylation reagents.
Assuntos
Aspirina/química , Ubiquitinas/química , Acetilação , Aspirina/síntese química , Isótopos de Carbono , Cinética , Espectroscopia de Ressonância Magnética , Ubiquitinas/análogos & derivadosRESUMO
Impermeable, solid polysulfone intracorneal lenses (ICLs) can change corneal refractive power but will not allow diffusion of nutrients from the aqueous to the anterior stroma. Lenses of 4, 5, 6, and 7 mm in diameter were implanted in 50 cat eyes at depths ranging from 45% to 95% of corneal thickness to determine the effect of depth and diameter. Two types of stromal opacities occurred during follow-up: peripheral amorphous opacity (100%) and crystalline-granular lipid central opacity (79%). No eyes implanted with a 4-mm ICL ulcerated, but ulceration occurred in 28% of the eyes overall. Because opacification occurred with all lens diameters and implantation depths, metabolic demands of the cornea are not met. No safe limit exists at which these ICLs can be predictably used in cat eyes.
Assuntos
Lentes Intraoculares , Polímeros/uso terapêutico , Sulfonas/uso terapêutico , Animais , Gatos , Córnea/análise , Opacidade da Córnea/patologia , Lipídeos/análiseRESUMO
A novel "multicoaxial hollow fiber bioreactor" has been developed consisting of four concentric tubes, the two innermost tubes are called hollow fibers. Bioartificial livers are created by culturing liver progenitors in the space between the two innermost hollow fibers and with culture media contained in the two compartments (intracapillary and extracapillary) sandwiching the cell compartment. The outermost compartment is used for gas exchange. A hydrodynamic model has recently been established to predict the optimum hydraulic permeability and bioreactor operational parameters to create the physicochemical environment found in the liver acinus. However, perfusion with serum-free hormonally-defined media and inoculation of cells introduces membrane fouling into the equation, and this parameter must be incorporated into the model. Using commercially available semipermeable hollow fibers (1 mm [0.65 microm pores] and 3 mm [0.1 microm pores] outer diameters [o.d]), the primary cause of resistance is the middle hollow fiber. Preliminary studies using bioreactors inoculated with isolated rat hepatocytes and perfused with serum-containing culture media demonstrated that the middle hollow fiber is the primary site of fouling, and this fouling ultimately causes cell mortality by blocking the transfer of nutrients. Experiments were performed to determine the best commercially available middle hollow fiber for construction of bioreactors and two 3-mm outer-diameter middle hollow fibers were compared: polypropylene and polysulfone, with 0.2 microm and 0.1 microm pore sizes, respectively. Dead-ended and cross flow configurations were compared for their effectiveness at reducing membrane fouling in the middle hollow fiber by determining the change in resistance with time. The results demonstrate that the 0.2-microm pore size polypropylene hollow fiber is the best choice for construction of the multicoaxial hollow-fiber bioreactor, and that cross flow results in two orders of magnitude lower resistance than dead-ended flow after 36 h.
Assuntos
Órgãos Bioartificiais , Fígado Artificial , Membranas Artificiais , Animais , Reatores Biológicos , Hepatócitos/ultraestrutura , Microscopia Eletrônica de Varredura , RatosRESUMO
OBJECTIVES: This study was designed to determine whether citrate levels detected by localized 1H spectroscopy could reliably discriminate regions of prostate adenocarcinoma from surrounding regions of normal peripheral zone and benign prostatic hyperplasia (BPH). METHODS: In 28 patients and 5 volunteers stimulated echo proton spectroscopy was used in conjunction with endorectal surface coils to obtain water-suppressed 1H spectra from regions of normal prostate peripheral zone, BPH, and prostate cancer. 1H spectra from prostate cancer patients were correlated with pathologic areas identified on T2-weighted endorectal coil magnetic resonance (MR) images and histologic study of the step-sectioned gland after surgery. RESULTS: The major finding of in vivo studies was consistently lower citrate levels in prostate cancer compared with BPH and normal prostate peripheral zone. This was reflected by significantly (P < 0.05) lower mean citrate/(creatine plus choline) peak area ratio observed for regions of cancer (0.67 +/- 0.17) compared with BPH (1.21 +/- 0.29) and normal peripheral zone (1.46 +/- 0.28). Moreover, there was no overlap of individual cancer and normal peripheral zone citrate ratios and no significant difference between citrate ratios in regions of normal peripheral zone in young volunteers (1.28 +/- 0.14) and age-matched patients (1.46 +/- 0.28). The observed alterations in vivo citrate levels were supported by citrate concentration data obtained from extracts of histologically proven samples of normal, benign, and malignant prostatic tissues removed at surgery. In vitro citrate levels in the normal peripheral zone (30.9 +/- 8.5 mumol/g wet weight) and BPH (46.3 +/- 5.4 mumol/g wet weight) were significantly higher than those for prostate cancer (3.74 +/- 0.54 mumol/g wet weight). CONCLUSIONS: These studies further demonstrate the potential of citrate as an in vivo marker for discriminating prostate cancer from surrounding regions of normal peripheral zone and BPH.
Assuntos
Adenocarcinoma/diagnóstico , Citratos/análise , Espectroscopia de Ressonância de Spin Eletrônica , Hiperplasia Prostática/diagnóstico , Neoplasias da Próstata/diagnóstico , Adenocarcinoma/química , Idoso , Biomarcadores/análise , Estudos de Casos e Controles , Ácido Cítrico , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Próstata/química , Neoplasias da Próstata/químicaRESUMO
Corneal thickness is a reflection of endothelial barrier and pump functions. The corneal edema that occurs during intraocular inflammation is a consequence of the breakdown of one or both of these parameters. Results of this study demonstrate that, during intraocular inflammation induced by an intravitreal injection of bovine serum albumin (BSA), the permeability of rabbit corneal endothelia to inulin was increased. By comparison, treatment with oral aspirin and/or subconjunctival triamcinolone acetonide prevented the endothelial barrier breakdown induced by the BSA. Concomitant with the loss of the barrier function, endothelial ouabain binding decreased in the BSA injected eye, indicating a reduction in endothelial Na/K ATPase pump site density. A subconjunctival injection of triamcinolone prevented this decrease in pump sites. The increase in endothelial permeability and the decrease in pump site density correlated with an increase in corneal thickness. It can be concluded that the intraocular inflammation induced by BSA effects corneal edema by both an increase in endothelial permeability and a decrease in Na/K ATPase pump site density. Subconjunctival triamcinolone is effective in preventing this response.
Assuntos
Endoftalmite/fisiopatologia , Endotélio Corneano/fisiopatologia , Animais , Bovinos , Contagem de Células , Córnea/patologia , Endoftalmite/induzido quimicamente , Endoftalmite/metabolismo , Endoftalmite/patologia , Endotélio Corneano/metabolismo , Ouabaína/metabolismo , Permeabilidade , Coelhos , Albumina SéricaRESUMO
This report describes the follow-up of a community-sponsored smoking cessation contest. The aims of the evaluation were to describe the characteristics of contestants and the quit rates at six weeks, six months and one year. The "Quit to Win" contest was held as part of a larger cancer prevention program in Medicine Hat, Alberta. In order to be eligible for prizes, contestants were required to be smoke-free for six weeks and have their smoking status verified by a "Buddy". Contestants were contacted by telephone at the end of the contest and again at six months and one year. Seventy-five individuals entered the contest. The quit rates, 56%, 27% and 21% at six weeks, six months and one year respectively, compare favourably with other smoking cessation interventions. This study demonstrates that a community-based program can reach a variety of smokers with a relatively simple intervention.
Assuntos
Serviços de Saúde Comunitária/organização & administração , Administração em Saúde Pública , Abandono do Hábito de Fumar/métodos , Prevenção do Hábito de Fumar , Adulto , Alberta/epidemiologia , Comportamento Competitivo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Prevalência , Avaliação de Programas e Projetos de Saúde , Fumar/epidemiologia , Fumar/psicologia , Abandono do Hábito de Fumar/psicologiaRESUMO
OBJECTIVE: To determine whether administration of endotoxin affects thyroid gland function in dogs. ANIMALS: 24 Beagles. PROCEDURE: Dogs were given thyrotropin (TSH) or thyrotropin-releasing hormone (TRH) on 2 occasions. Twenty-four hours before the second challenge with TSH or TRH, all dogs were given 5 micrograms of endotoxin/kg of body weight. Serum concentrations of thyroxine (T4), free T4 (fT4), 3,3',5-triiodothyronine (T3), reverse T3, autoantibodies to T3, and plasma concentrations of ACTH and cortisol were determined. RESULTS: Treatment with endotoxin was associated with reduced baseline concentration of serum T3 and increased baseline concentration of reverse T3 and free T4. Endotoxin treatment resulted in reduced peak serum concentration of T4 after TSH and TRH. However, peak serum concentration of fT4 after TSH and TRH were not affected by endotoxin. CONCLUSIONS: A single dose of endotoxin affects several aspects of thyroid gland function in dogs, including T4 binding, deiodinase activity, and the thyroidal response to TSH and TRH. CLINICAL RELEVANCE: Acute or chronic nonthyroidal illness may affect thyroid gland function in dogs. Determination of fT4 concentration may provide a means of differentiating the effects of nonthyroidal illness from those of thyroid dysfunction, because endotoxin treatment was associated with increased baseline serum free T4 concentration and unchanged peak serum fT4 concentration after administration of TSH or TRH.
Assuntos
Endotoxinas/toxicidade , Glândula Tireoide/fisiologia , Hormônio Liberador de Tireotropina/farmacologia , Tireotropina/farmacologia , Tiroxina/sangue , Tri-Iodotironina/sangue , Hormônio Adrenocorticotrópico/sangue , Animais , Cães , Feminino , Hidrocortisona/sangue , Masculino , Análise de Regressão , Glândula Tireoide/efeitos dos fármacos , Tiroxina/metabolismo , Fatores de Tempo , Tri-Iodotironina/metabolismo , Tri-Iodotironina Reversa/sangue , Tri-Iodotironina Reversa/metabolismoRESUMO
Cefadroxil was found to be an effective antibiotic for the treatment of canine bacterial pyoderma. Bacterial pyoderma was diagnosed in 30 dogs, which were treated with cefadroxil administered orally at 22 mg/kg of body weight, q 12 h, for 21 to 30 days. Dogs were reexamined at the conclusion of antibiotic treatment, and 29 were found to have good to excellent response. On the basis of this study, cefadroxil is a good choice in the treatment of canine pyoderma when cephalosporins are necessary. Efficacy, frequency of administration, cost, and veterinary approval are the major advantages.
Assuntos
Infecções Bacterianas/veterinária , Cefadroxila/uso terapêutico , Dermatite/veterinária , Doenças do Cão/tratamento farmacológico , Pioderma/veterinária , Animais , Infecções Bacterianas/tratamento farmacológico , Cefadroxila/efeitos adversos , Dermatite/tratamento farmacológico , Cães , Feminino , Masculino , Pioderma/tratamento farmacológicoRESUMO
Medical records were reviewed for 18 cats with adenomatous polyps of the proximal portion of the duodenum. Cats of Asian ancestry were over represented (8/18), and male castrated cats were common (15/18). The median age was 11.8 years. Common clinical signs were acute and chronic vomiting and hematemesis. Nine cats were anemic. Contrast radiography was performed in 12 cats, and a mass of the proximal portion of the duodenum was identified in 10 cats. Endoscopy was used to confirm existence of the mass in 3 cats. Complete excision of the duodenal mass was performed in 17 cats. One cat died before abdominal exploratory surgery, and a duodenal adenomatous polyp was identified at necropsy. Fifteen cats survived the immediate postoperative period, with 13 of 15 having complete resolution of clinical signs. Five cats had concurrent disease, which caused 4 of them to die between 3 and 26 months after surgery. Redevelopment of adenomatous polyps was not detected in any cat during the follow-up period of 1 to 49 months. Results of the study indicated that benign, adenomatous polyps of the duodenum in cats can be safely excised and that the prognosis for return to normal function is excellent.
Assuntos
Doenças do Gato , Neoplasias Duodenais/veterinária , Pólipos Intestinais/veterinária , Animais , Cruzamento , Doenças do Gato/patologia , Doenças do Gato/cirurgia , Gatos , Neoplasias Duodenais/patologia , Neoplasias Duodenais/cirurgia , Feminino , Seguimentos , Pólipos Intestinais/patologia , Pólipos Intestinais/cirurgia , Masculino , Estudos RetrospectivosRESUMO
We describe the management of two patients with severe heart dysfunction requiring caesarean section because of incipient left ventricular failure. One patient had a bicuspid valve and developed symptoms of severe aortic incompetence during pregnancy. The second patient had known hypertrophic obstructive cardiomyopathy and developed chest pain and symptoms of left ventricular failure at 32 weeks' gestation. In both cases the worsening cardiac disease prompted the decision for operative delivery. We decided to employ general anaesthesia and achieved cardiovascular stability using remifentanil as an adjunct.
RESUMO
As the science of wound healing has evolved in the past two decades, so has awareness of the "hidden epidemic" of lymphedema. Substantial information has been accumulated regarding the pathophysiology and therapy of lymphedema. However, until now, the relationship between wound care and lymphedema has received little attention. This review outlines this relationship and asserts that proper wound care demands attention to the related lymphedema. The differences between edema and lymphedema, as well as current evidence-based support defining the negative effect of lymphedema on wound healing, are discussed. The principles of compression therapy in wound related lymphedema also are addressed.
Assuntos
Linfedema , Especialidade de Fisioterapia/métodos , Cicatrização , Edema/fisiopatologia , Humanos , Linfedema/fisiopatologia , Linfedema/reabilitação , Úlcera Varicosa/reabilitaçãoRESUMO
After neuronal injury or death glial cells become reactive, exhibiting dramatic changes in morphology and patterns of gene expression and ultimately engulfing neuronal debris. Rapid clearance of degenerating neuronal material is thought to be crucial for suppression of inflammation and promotion of functional recovery. Here we demonstrate that Drosophila c-Jun N-terminal kinase (dJNK) signaling is a critical in vivo mediator of glial engulfment activity. In response to axotomy, we find glial dJNK signals through a cascade involving the upstream mitogen-activated protein kinase kinase kinases Slipper and Tak1, the mitogen-activated protein kinase kinase MKK4, and ultimately the Drosophila activator protein 1 (AP-1) transcriptional complex composed of Jra and Kayak to initiate glial phagocytosis of degenerating axons. Interestingly, loss of dJNK also blocked injury-induced upregulation of Draper levels in glia, and glial-specific overexpression of Draper was sufficient to rescue engulfment defects associated with loss of dJNK signaling. This work identifies that the dJNK pathway is a novel mediator of glial engulfment activity and a primary role for the glial Slipper/Tak1 âMKK4 âdJNK âdAP-1 signaling cascade appears to be activation of draper expression after axon injury.
Assuntos
Proteínas de Drosophila/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Proteínas de Membrana/metabolismo , Neuroglia/metabolismo , Fagocitose/genética , Animais , Apoptose , Axônios/metabolismo , Axotomia , Encéfalo/metabolismo , Lesões Encefálicas/genética , Lesões Encefálicas/metabolismo , Drosophila , Proteínas de Drosophila/biossíntese , Proteínas de Drosophila/genética , Proteínas Quinases JNK Ativadas por Mitógeno/genética , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , MAP Quinase Quinase Quinases/genética , MAP Quinase Quinase Quinases/metabolismo , Proteínas de Membrana/biossíntese , Proteínas de Membrana/genética , Neuroglia/citologia , Interferência de RNA , RNA Interferente Pequeno , Transdução de Sinais/genética , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismoRESUMO
AIM: Leg compression bandaging is the mainstay of venous ulcer treatment, yet little is known about the impact of therapeutic compression levels on arterial haemodynamics. In this study, the effect of foot-to-knee, four-layer compression bandaging on below-knee arterial pulsatile blood flow was assessed by nuclear magnetic resonance flowmetry. METHODS: In 14 healthy supine subjects, bilateral pulsatile blood flow measured at five below-knee sites without compression; and during compression of one leg to an average malleolar sub-bandage pressure of 40.7±4.0 mmHg. RESULTS: The forefoot-to-knee compression bandaging caused a highly significant (P<0.001) increase in the bandaged leg pulsatile blood flow due to increases in both peak flow and pulse width. CONCLUSION: It is hypothesized that arteriolar vasodilatation, induced either myogenically by reduced transmural pressure or by vasodilatory substance release triggered by increased venous shear stress and veno-arterial interactions, possibly combined with altered vascular compliance, produce the observed compression-related phenomenon. Whatever the mechanism(s), the finding of a compression-associated pulsatile flow increase suggests an arterial linkage, which may play a role in the well-documented beneficial effects of compression bandaging in venous ulcer and lymphedema treatment. Possible beneficial effects of the arterial flow-pulse increase on venous ulcer outcome may be related to a decrease in leukocyte effects in the distal microvasculature.