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OBJECTIVES: To 1) determine the types and frequency of complications within 3 months following ultrasound-guided surgical procedures, and 2) identify any patient demographics, co-morbidities, or procedural characteristics that were associated with an increased risk of complications. METHODS: A retrospective chart review was performed at six Sports Medicine clinics across the United States. The Clavien-Dindo classification was used to categorize procedural complications on a 5-point scale from 1, representing any deviation in post-procedure care without requiring pharmacological or invasive treatment to 5, representing death. Generalized Estimating Equations for binomial outcomes with a logit link were used to estimate the overall and procedure-specific 3-month complication rates. RESULTS: Among 1902 patients, 8.1% (n = 154) had diabetes and 6.3% (n = 119) were current smokers. The analysis included 2,369 procedures, which were performed in either the upper extremity (44.1%, n = 1045) or lower extremity (55.2%, n = 1308) regions. The most common procedure was ultrasound-guided tenotomy (69.9%, n = 1655). Additional procedures included, trigger finger release (13.1%, n = 310), tendon scraping (8.0%, n = 189), carpal tunnel release (5.4%, n = 128), soft tissue release (2.1%, n = 50), and compartment fasciotomy (1.6%, n = 37). Overall, there was a complication rate of 1.2% (n = 29 complications; 95% CI: 0.8-1.7%). Individual procedures had complication rates that ranged from 0 to 2.7%. There were 13 Grade I complications in 13 patients, 12 Grade II complications in 10 patients, 4 Grade III complications in 4 patients, and 0 Grade IV or V complications. No associations between complication risk and any patient demographics (age, sex, BMI), co-morbidities (diabetes, smoker), or procedure characteristics (type, region) were identified. CONCLUSION: This retrospective review provides an evidence-based estimate supporting the low level of risk associated with ultrasound-guided surgical procedures for patients from a variety of geographical settings who are seeking care at private and academic-affiliated clinics.
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BACKGROUND: Brain-derived neurotrophic factor (BDNF) exerts its effects on neural plasticity via 2 distinct receptor types, the tyrosine kinase TrkB and the p75 neurotrophin receptor (p75NTR). The latter can promote inflammation and cell death while TrkB is critically involved in plasticity and memory, particularly in the hippocampus. Acute and chronic stress have been associated with suppression of hippocampal BDNF expression and impaired hippocampal plasticity. We hypothesized that p75NTR might be involved in the hippocampal stress response, in particular in stress-induced BDNF suppression, which might be accompanied by increased neuroinflammation. METHOD: We assessed hippocampal BDNF protein concentrations in wild-type mice compared that in mice lacking the long form of the p75NTR (p75NTRExIII-/-) with or without prior exposure to a 1-hour restraint stress challenge. Hippocampal BDNF concentrations were measured using an optimized ELISA. Furthermore, whole-brain mRNA expression of pro-inflammatory interleukin-6 (Il6) was assessed with RT-PCR. RESULTS: Deletion of full-length p75NTR was associated with higher hippocampal BDNF protein concentration in the stress condition, suggesting persistently high hippocampal BDNF levels in p75NTR-deficient mice, even under stress. Stress elicited increased whole-brain Il6 mRNA expression irrespective of genotype; however, p75NTRExIII-/- mice showed elevated baseline Il6 expression and thus a lower relative increase. CONCLUSIONS: Our results provide evidence for a role of p75NTR signaling in the regulation of hippocampal BDNF levels, particularly under stress. Furthermore, p75NTR signaling modulates baseline but not stress-related Il6 gene expression in mice. Our findings implicate p75NTR signaling as a potential pathomechanism in BDNF-dependent modulation of risk for neuropsychiatric disorders.
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Factor Neurotrófico Derivado del Encéfalo , Receptor de Factor de Crecimiento Nervioso , Animales , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Hipocampo/metabolismo , Ratones , Receptor de Factor de Crecimiento Nervioso/metabolismo , Receptores de Factor de Crecimiento Nervioso/genética , Receptores de Factor de Crecimiento Nervioso/metabolismo , Transducción de SeñalRESUMEN
Mice with impaired acute inflammatory responses within adipose tissue display reduced diet-induced fat mass gain associated with glucose intolerance and systemic inflammation. Therefore, acute adipose tissue inflammation is needed for a healthy expansion of adipose tissue. Because inflammatory disorders are associated with bone loss, we hypothesized that impaired acute adipose tissue inflammation leading to increased systemic inflammation results in a lower bone mass. To test this hypothesis, we used mice overexpressing an adenoviral protein complex, the receptor internalization and degradation (RID) complex that inhibits proinflammatory signaling, under the control of the aP2 promotor (RID tg mice), resulting in suppressed inflammatory signaling in adipocytes. As expected, RID tg mice had lower high-fat diet-induced weight and fat mass gain and higher systemic inflammation than littermate wild-type control mice. Contrary to our hypothesis, RID tg mice had increased bone mass in long bones and vertebrae, affecting trabecular and cortical parameters, as well as improved humeral biomechanical properties. We did not find any differences in bone formation or resorption parameters as determined by histology or enzyme immunoassay. However, bone marrow adiposity, often negatively associated with bone mass, was decreased in male RID tg mice as determined by histological analysis of tibia. In conclusion, mice with reduced fat mass due to impaired adipose tissue inflammation have increased bone mass.
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Tejido Adiposo/diagnóstico por imagen , Densidad Ósea/fisiología , Huesos/diagnóstico por imagen , Inflamación/metabolismo , Absorciometría de Fotón , Tejido Adiposo/metabolismo , Animales , Biomarcadores/sangre , Huesos/metabolismo , Colágeno Tipo I/sangre , Modelos Animales de Enfermedad , Inflamación/sangre , Inflamación/diagnóstico por imagen , Ratones , Fragmentos de Péptidos/sangre , Péptidos/sangre , Procolágeno/sangre , Transducción de Señal/genética , Microtomografía por Rayos XRESUMEN
Ultrasound-guided carpal tunnel release was performed on 14 patients (18 wrists) using dynamic expansion of the transverse safe zone. Our patient population included able-bodied patients and those with impairments. The first 8 cases (12 wrists) underwent the procedure in an operating room, the remainder in an outpatient setting. No complications occurred, and all patients were able to immediately resume use of their hands without therapy. Improvements in the Quick Form of the Disabilities of the Arm, Shoulder, and Hand Index and Boston Carpal Tunnel Questionnaire at 3 months were comparable to results reported with mini-open and endoscopic release. Our results show that ultrasound-guided carpal tunnel release can be safely and effectively performed in an outpatient setting.
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Síndrome del Túnel Carpiano/diagnóstico por imagen , Síndrome del Túnel Carpiano/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Ultrasonografía Intervencional/métodos , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Nervio Mediano/diagnóstico por imagen , Nervio Mediano/cirugía , Persona de Mediana Edad , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Surgical transection of sensory nerves in the treatment of intractable neuropathic pain is a commonly performed procedure. At times these cases can be particularly challenging when encountering obese patients, when targeting deeper nerves or those with a variable branching pattern, or in the case of repeat operations. In this case series, the authors describe their experience with ultrasound-guided surgical instrument placement during transection of a saphenous nerve in the region of prior vascular surgery in 1 patient and in the lateral femoral cutaneous nerve in 2 obese patients. The authors also describe this novel technique and provide pilot data that suggests ultrasound-assisted surgery may allow for complex cases to be completed in an expedited fashion through smaller incisions.
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Monitoreo Intraoperatorio/métodos , Neuralgia/diagnóstico por imagen , Neuralgia/cirugía , Enfermedades del Sistema Nervioso Periférico/diagnóstico por imagen , Enfermedades del Sistema Nervioso Periférico/cirugía , Ultrasonografía Intervencional/métodos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , SíndromeRESUMEN
OBJECTIVES: The purpose of this study was to compare ultrasound-guided percutaneous tendon fenestration to platelet-rich plasma (PRP) injection for treatment of greater trochanteric pain syndrome. METHODS: After Institutional Review Board approval was obtained, patients with symptoms of greater trochanteric pain syndrome and ultrasound findings of gluteal tendinosis or a partial tear (<50% depth) were blinded and treated with ultrasound-guided fenestration or autologous PRP injection of the abnormal tendon. Pain scores were recorded at baseline, week 1, and week 2 after treatment. Retrospective clinic record review assessed patient symptoms. RESULTS: The study group consisted of 30 patients (24 female), of whom 50% were treated with fenestration and 50% were treated with PRP. The gluteus medius was treated in 73% and 67% in the fenestration and PRP groups, respectively. Tendinosis was present in all patients. In the fenestration group, mean pain scores were 32.4 at baseline, 16.8 at time point 1, and 15.2 at time point 2. In the PRP group, mean pain scores were 31.4 at baseline, 25.5 at time point 1, and 19.4 at time point 2. Retrospective follow-up showed significant pain score improvement from baseline to time points 1 and 2 (P< .0001) but no difference between treatment groups (P= .1623). There was 71% and 79% improvement at 92 days (mean) in the fenestration and PRP groups, respectively, with no significant difference between the treatments (P >.99). CONCLUSIONS: Our study shows that both ultrasound-guided tendon fenestration and PRP injection are effective for treatment of gluteal tendinosis, showing symptom improvement in both treatment groups.
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Fémur , Manejo del Dolor/métodos , Transfusión de Plaquetas/métodos , Plasma Rico en Plaquetas , Tendinopatía/terapia , Tenotomía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Dolor , Estudios Prospectivos , Síndrome , Tendones , Resultado del Tratamiento , Ultrasonografía Intervencional , Adulto JovenRESUMEN
Strain engineering beyond substrate limitation of colossal magnetoresistant thin (La0.6Pr0.4)0.7Ca0.3MnO3 (LPCMO) films on LaAlO3-buffered SrTiO3 (LAO/STO) substrates has been demonstrated using metalorganic aerosol deposition technique. By growing partially relaxed 7-27 nm thick heteroepitaxial LAO buffer layers on STO a perfect lattice matching to the LPCMO has been achieved. As a result, strain-free heteroepitaxial 10-20 nm thick LPCMO/LAO/STO films with bulk-like ferromagnetic metallic ground state were obtained. Without buffer the coherently strained thin LPCMO/STO and LPCMO/LAO films were insulating and weakly magnetic. The reason for the optimized magnetotransport in strain-free LPCMO films was found to be a large octahedral Mn-O-Mn bond angle φOOR ~ 166-168° as compared to the significantly smaller one of φOOR ~ 152-156° determined for the tensile (LPCMO/STO) and compressively (LPCMO/LAO) strained films.
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This study investigated the effect of using the lactate-utilizing bacterium Megasphaera elsdenii NCIMB 41125 as a probiotic supplement on rumen fermentation and pH in dairy cows in the immediate postcalving period. Fourteen multiparous rumen-fistulated Holstein cows, blocked according to 305-d milk yield in the previous lactation, were used in a randomized complete block design. From d 1 to 28 postcalving, cows were fed ad libitum a total mixed ration with a forage to concentrate ratio of 392:608 and a starch concentration of 299g/kg of dry matter. Treatments consisting of a minimum of 10(10) cfu of Megasphaera elsdenii NCIMB 41125 or autoclaved M. elsdenii (placebo) were administered via the rumen cannula on d 3 and 12 of lactation (n=7 per treatment). Mid-rumen pH was measured every 15min, and eating and ruminating behaviors were recorded for 24h on d 2, 4, 6, 8, 11, 13, 15, 17, 22, and 28. Rumen fluid for volatile fatty acid and lactic acid analysis was collected at 11 time points on each of d 2, 4, 6, 13, and 15. Yields of milk and milk protein and lactose were similar, but milk fat concentration tended to be higher in cows that received the placebo. Time spent eating and ruminating and dry matter intake were similar across treatments. Ruminal lactic acid concentrations were highly variable between animals, and no cases of clinical acidosis were observed. Both treatment groups had rumen pH <5.6 for more than 3h/d (a commonly used threshold to define subacute ruminal acidosis), but the length of time with rumen pH <5.6 was markedly reduced in the days immediately after dosing and fluctuated much less from day to day in cows that received M. elsdenii compared with those that received the placebo. Ruminal total volatile fatty acid concentrations were similar across treatments, but the acetate:propionate ratio tended to be smaller in cows that received M. elsdenii. Despite the lack of a measurable treatment effect on ruminal lactic acid concentration, supplementation of early lactation dairy cows with lactate-utilizing M. elsdenii altered the rumen fermentation patterns in favor of propionate, with potential benefits for energy balance and animal productivity.
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Bovinos/fisiología , Fermentación/fisiología , Lactancia/fisiología , Megasphaera/fisiología , Probióticos , Rumen , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Bovinos/metabolismo , Bovinos/microbiología , Femenino , Concentración de Iones de Hidrógeno , Leche/metabolismo , Periodo Posparto , Embarazo , Rumen/química , Rumen/metabolismo , Rumen/microbiología , Factores de TiempoRESUMEN
Most of the fascinating phenomena studied in cell biology emerge from interactions among highly organized multimolecular structures embedded into complex and frequently dynamic cellular morphologies. For the exploration of such systems, computer simulation has proved to be an invaluable tool, and many researchers in this field have developed sophisticated computational models for application to specific cell biological questions. However, it is often difficult to reconcile conflicting computational results that use different approaches to describe the same phenomenon. To address this issue systematically, we have defined a series of computational test cases ranging from very simple to moderately complex, varying key features of dimensionality, reaction type, reaction speed, crowding, and cell size. We then quantified how explicit spatial and/or stochastic implementations alter outcomes, even when all methods use the same reaction network, rates, and concentrations. For simple cases, we generally find minor differences in solutions of the same problem. However, we observe increasing discordance as the effects of localization, dimensionality reduction, and irreversible enzymatic reactions are combined. We discuss the strengths and limitations of commonly used computational approaches for exploring cell biological questions and provide a framework for decision making by researchers developing new models. As computational power and speed continue to increase at a remarkable rate, the dream of a fully comprehensive computational model of a living cell may be drawing closer to reality, but our analysis demonstrates that it will be crucial to evaluate the accuracy of such models critically and systematically.
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Células/metabolismo , Simulación por Computador , División Celular , Relojes Circadianos/genética , Difusión , Retroalimentación Fisiológica , Regulación de la Expresión Génica , Fosforilación , Unión Proteica , Procesos Estocásticos , Factores de TiempoRESUMEN
The adhesion and degranulation-promoting adaptor protein (ADAP) serves as a multifunctional scaffold and is involved in the formation of immune signaling complexes. To date, only limited data exist regarding the role of ADAP in pathogen-specific immunity during in vivo infection, and its contribution in phagocyte-mediated antibacterial immunity remains elusive. Here, we show that mice lacking ADAP (ADAPko) are highly susceptible to the infection with the intracellular pathogen Listeria monocytogenes (Lm) by showing enhanced immunopathology in infected tissues together with increased morbidity, mortality, and excessive infiltration of neutrophils and monocytes. Despite high phagocyte numbers in the spleen and liver, ADAPko mice only inefficiently controlled pathogen growth, hinting at a functional impairment of infection-primed phagocytes in the ADAP-deficient host. Flow cytometric analysis of hallmark pro-inflammatory mediators and unbiased whole genome transcriptional profiling of neutrophils and inflammatory monocytes uncovered broad molecular alterations in the inflammatory program in both phagocyte subsets following their activation in the ADAP-deficient host. Strikingly, ex vivo phagocytosis assay revealed impaired phagocytic capacity of neutrophils derived from Lm-infected ADAPko mice. Together, our data suggest that an alternative priming of phagocytes in ADAP-deficient mice during Lm infection induces marked alterations in the inflammatory profile of neutrophils and inflammatory monocytes that contribute to enhanced immunopathology while limiting their capacity to eliminate the pathogen and to prevent the fatal outcome of the infection.
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Proteínas Adaptadoras Transductoras de Señales/genética , Listeria monocytogenes/inmunología , Listeriosis/inmunología , Fagocitos/inmunología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Femenino , Inmunidad , Listeriosis/metabolismo , Listeriosis/microbiología , Hígado/metabolismo , Masculino , Ratones , Ratones Noqueados , Fagocitos/metabolismo , Fenotipo , Bazo/metabolismoRESUMEN
Vectors based on Adenovirus type 5 (Ad5) are among the most common vectors in cancer gene therapy trials to date. However, for increased efficiency and safety, Ad5 should be de-targeted from its native receptors and re-targeted to a tumor antigen. We have described earlier an Ad5 vector genetically re-targeted to the tumor antigen HER2/neu by a dimeric version of the Affibody molecule ZH inserted in the HI-loop of the fiber knob of a coxsackie and adenovirus receptor-binding ablated fiber. This virus showed almost wild-type growth characteristics and infected cells through HER2/neu. Here we generate vectors with double specificity by incorporating two different Affibody molecules, ZH (HER2/neu-binding) and ZT (Taq polymerase-binding), at different positions relative to one another in the HI-loop. Receptor-binding studies together with viral production and gene transfer assays showed that the recombinant fiber with ZT in the first position and ZH in the second position (ZTZH) bound to both its targets, whereas surprisingly, the fiber with ZHZT was devoid of binding to HER2/neu. Hence, it is possible to construct a recombinant adenovirus with dual specificity after evaluating the best position for each ligand in the fiber knob.
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Adenoviridae/genética , Marcación de Gen/métodos , Terapia Genética/métodos , Vectores Genéticos/genética , Adenoviridae/fisiología , Línea Celular , Humanos , Ligandos , Multimerización de Proteína , Proteínas Recombinantes de Fusión/biosíntesis , Recombinación Genética , Solubilidad , Transfección , Replicación ViralRESUMEN
Carpal tunnel syndrome is the most common entrapment neuropathy, resulting in 500,000 carpal tunnel release (CTR) surgeries and a total cost of more than 2 billion dollars annually in the United States. Although initially performed via a large (3-5 cm) palmar incision, CTR techniques have continually evolved to reduce incision size, recovery times, postoperative pain, and improve cosmesis and clinical outcomes. More recently, multiple authors have reported excellent results after ultrasound-guided carpal tunnel release (USCTR) using a variety of techniques, and one prospective randomized trial reported faster recovery after USCTR compared with traditional mini-open CTR. However, there is a paucity of data with respect to changes in the median nerve after USCTR. This case report presents the functional outcomes and pre- and postprocedure ultrasound images of a patient after USCTR with 3-month follow-up. LEVEL OF EVIDENCE: V.
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Síndrome del Túnel Carpiano/diagnóstico por imagen , Síndrome del Túnel Carpiano/cirugía , Ligamentos Articulares/cirugía , Cirugía Asistida por Computador/métodos , Ultrasonografía Doppler en Color/métodos , Anciano , Descompresión Quirúrgica/métodos , Estudios de Seguimiento , Humanos , Masculino , Nervio Mediano/cirugía , Dimensión del Dolor , Medición de Riesgo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Estrogen treatment has positive effects on the skeleton, and we have shown that estrogen receptor alpha (ERα) expression in cells of hematopoietic origin contributes to a normal estrogen treatment response in bone tissue. T lymphocytes are implicated in the estrogenic regulation of bone mass, but it is not known whether T lymphocytes are direct estrogen target cells. Therefore, the aim of this study was to determine the importance of ERα expression in T lymphocytes for the estrogenic regulation of the skeleton using female mice lacking ERα expression specifically in T lymphocytes (Lck-ERα-/-) and ERαflox/flox littermate (control) mice. Deletion of ERα expression in T lymphocytes did not affect bone mineral density (BMD) in sham-operated Lck-ERα-/- compared to control mice, and ovariectomy (ovx) resulted in a similar decrease in BMD in control and Lck-ERα-/- mice compared to sham-operated mice. Furthermore, estrogen treatment of ovx Lck-ERα-/- led to an increased BMD that was indistinguishable from the increase seen after estrogen treatment of ovx control mice. Detailed analysis of both the appendicular (femur) and axial (vertebrae) skeleton showed that both trabecular and cortical bone parameters responded to a similar extent regardless of the presence of ERα in T lymphocytes. In conclusion, ERα expression in T lymphocytes is dispensable for normal estrogenic regulation of bone mass in female mice.
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Huesos/efectos de los fármacos , Receptor alfa de Estrógeno/genética , Estrógenos/farmacología , Linfocitos T/metabolismo , Animales , Densidad Ósea/efectos de los fármacos , Densidad Ósea/genética , Huesos/metabolismo , Receptor alfa de Estrógeno/metabolismo , Femenino , Expresión Génica , Silenciador del Gen , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Especificidad de Órganos/genética , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genéticaRESUMEN
The importance of estrogen receptor α (ERα) for the regulation of bone mass in males is well established. ERα mediates estrogenic effects both via nuclear and membrane-initiated ERα (mERα) signaling. The role of mERα signaling for the effects of estrogen on bone in male mice is unknown. To investigate the role of mERα signaling, we have used mice (Nuclear-Only-ER; NOER) with a point mutation (C451A), which results in inhibited trafficking of ERα to the plasma membrane. Gonadal-intact male NOER mice had a significantly decreased total body areal bone mineral density (aBMD) compared to WT littermates at 3, 6 and 9 months of age as measured by dual-energy X-ray absorptiometry (DEXA). High-resolution microcomputed tomography (µCT) analysis of tibia in 3-month-old males demonstrated a decrease in cortical and trabecular thickness in NOER mice compared to WT littermates. As expected, estradiol (E2) treatment of orchidectomized (ORX) WT mice increased total body aBMD, trabecular BV/TV and cortical thickness in tibia compared to placebo treatment. E2 treatment increased these skeletal parameters also in ORX NOER mice. However, the estrogenic responses were significantly decreased in ORX NOER mice compared with ORX WT mice. In conclusion, mERα is essential for normal estrogen signaling in both trabecular and cortical bone in male mice. Increased knowledge of estrogen signaling mechanisms in the regulation of the male skeleton may aid in the development of new treatment options for male osteoporosis.
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Huesos/metabolismo , Receptor alfa de Estrógeno/metabolismo , Estrógenos/metabolismo , Animales , Densidad Ósea , Remodelación Ósea , Masculino , RatonesRESUMEN
In order to use adenovirus (Ad) type 5 (Ad5) for cancer gene therapy, Ad needs to be de-targeted from its native receptors and re-targeted to a tumor antigen. A limiting factor for this has been to find a ligand that (i) binds a relevant target, (ii) is able to fold correctly in the reducing environment of the cytoplasm and (iii) when incorporated at an optimal position on the virion results in a virus with a low physical particle to plaque-forming units ratio to diminish the viral load to be administered to a future patient. Here, we present a solution to these problems by producing a genetically re-targeted Ad with a tandem repeat of the HER2/neu reactive Affibody molecule (ZH) in the HI-loop of a Coxsackie B virus and Ad receptor (CAR) binding ablated fiber genetically modified to contain sequences for flexible linkers between the ZH and the knob sequences. ZH is an Affibody molecule specific for the extracellular domain of human epidermal growth factor receptor 2 (HER2/neu) that is overexpressed in inter alia breast and ovarian carcinomas. The virus presented here exhibits near wild-type growth characteristics, infects cells via HER2/neu instead of CAR and represents an important step toward the development of genetically re-targeted adenoviruses with clinical relevance.
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Adenoviridae/genética , Antígenos de Neoplasias/genética , Terapia Genética/métodos , Vectores Genéticos/genética , Proteínas Recombinantes de Fusión/genética , Antígenos de Neoplasias/inmunología , Neoplasias de la Mama/terapia , Femenino , Humanos , Ligandos , Neoplasias Ováricas/terapia , Receptor ErbB-2/genética , Receptor ErbB-2/inmunología , Proteínas Recombinantes de Fusión/inmunología , Células Tumorales CultivadasRESUMEN
Cerebral toxoplasmosis is characterized by activation of brain resident cells and recruitment of specific immune cell subsets from the periphery to the central nervous system (CNS). Our studies revealed that the rapidly invaded Ly6G+ neutrophil granulocytes are an early non-lymphoid source of interferon-gamma (IFN-γ), the cytokine known to be the major mediator of host resistance to Toxoplasma gondii (T. gondii). Upon selective depletion of Ly6G+ neutrophils, we detected reduced IFN-γ production and increased parasite burden in the CNS. Ablation of Ly6G+ cells resulted in diminished recruitment of Ly6Chi monocytes into the CNS, indicating a pronounced interplay. Additionally, we identified infiltrated Ly6G+ neutrophils to be a heterogeneous population. The Ly6G+CD62-LhiCXCR4+ subset released cathelicidin-related antimicrobial peptide (CRAMP), which can promote monocyte dynamics. On the other hand, the Ly6G+CD62-LloCXCR4+ subset produced IFN-γ to establish early inflammatory response. Collectively, our findings revealed that the recruited Ly6G+CXCR4+ neutrophil granulocytes display a heterogeneity in the CNS with a repertoire of effector functions crucial in parasite control and immune regulation upon experimental cerebral toxoplasmosis.
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Sistema Nervioso Central/inmunología , Granulocitos/inmunología , Neutrófilos/inmunología , Toxoplasma/inmunología , Toxoplasmosis Cerebral/inmunología , Toxoplasmosis/inmunología , Animales , Encéfalo/inmunología , Encéfalo/parasitología , Encéfalo/patología , Sistema Nervioso Central/parasitología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Granulocitos/metabolismo , Interacciones Huésped-Parásitos/inmunología , Inflamación/inmunología , Interferón gamma/metabolismo , Ratones , Ratones Endogámicos C57BL , Microglía/inmunología , Microglía/metabolismo , Monocitos/inmunología , Infiltración Neutrófila , Neutrófilos/metabolismo , Especies Reactivas de Oxígeno/aislamiento & purificación , Receptores de Quimiocina/sangre , Toxoplasmosis Cerebral/parasitología , Toxoplasmosis Cerebral/patologíaRESUMEN
This article reviews commonly performed injections about the foot and ankle region. Although not exhaustive in its description of available techniques, general approaches to these procedures are applicable to any injection about the foot and ankle. As much as possible, the procedures described are based on commonly used or published techniques. An in-depth knowledge of the regional anatomy and understanding of different approaches when performing ultrasonography-guided procedures allows clinicians to adapt to any clinical scenario.
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Corticoesteroides/administración & dosificación , Articulación del Tobillo/diagnóstico por imagen , Ultrasonografía Intervencional/métodos , Anestésicos Locales/administración & dosificación , Bolsa Sinovial/diagnóstico por imagen , Antepié Humano/diagnóstico por imagen , Humanos , Inyecciones Intraarticulares/instrumentación , Inyecciones Intraarticulares/métodos , Articulación Metatarsofalángica/diagnóstico por imagen , Neuroma/diagnóstico por imagen , Neuroma/tratamiento farmacológico , Posicionamiento del Paciente , Tendones/diagnóstico por imagen , Ultrasonografía Intervencional/instrumentaciónRESUMEN
Estrogen receptor α (ERα) signaling leads to cellular responses in several tissues and in addition to nuclear ERα-mediated effects, membrane ERα (mERα) signaling may be of importance. To elucidate the significance, in vivo, of mERα signaling in multiple estrogen-responsive tissues, we have used female mice lacking the ability to localize ERα to the membrane due to a point mutation in the palmitoylation site (C451A), so called Nuclear-Only-ER (NOER) mice. Interestingly, the role of mERα signaling for the estrogen response was highly tissue-dependent, with trabecular bone in the axial skeleton being strongly dependent (>80% reduction in estrogen response in NOER mice), cortical and trabecular bone in long bones, as well as uterus and thymus being partly dependent (40-70% reduction in estrogen response in NOER mice) and effects on liver weight and total body fat mass being essentially independent of mERα (<35% reduction in estrogen response in NOER mice). In conclusion, mERα signaling is important for the estrogenic response in female mice in a tissue-dependent manner. Increased knowledge regarding membrane initiated ERα actions may provide means to develop new selective estrogen receptor modulators with improved profiles.
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Membrana Celular/metabolismo , Estradiol/farmacología , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Húmero/metabolismo , Tejido Adiposo/efectos de los fármacos , Animales , Membrana Celular/genética , Retroalimentación Fisiológica , Femenino , Lipoilación , Hígado/metabolismo , Ratones , Mutación , Tamaño de los Órganos/efectos de los fármacos , Especificidad de Órganos , Ovariectomía , Transducción de Señal , Timo/metabolismo , Útero/metabolismoRESUMEN
DNA-binding proteins have been extracted from the thermoacidophilic archaebacterium Sulfolobus solfataricus strain P1, grown at 86 degrees C and pH 4.5. These proteins, which may have a histone-like function, were isolated and purified under standard, non-denaturing conditions, and can be grouped into three molecular mass classes of 7, 8 and 10 kDa. We have purified to homogenity the main 7 kDa protein and determined its DNA-binding affinity by filter binding assays and electron microscopy. The Stokes radius of gyration indicates that the protein occurs as a monomer. The complete amino-acid sequence of this protein contains 14 lysine residues out of 63 amino acids and the calculated Mr is 7149. Five of the lysine residues are partially monomethylated to varying extents and the methylated residues are located exclusively in the N-terminal (positions 4 and 6) and the C-terminal (positions 60, 62 and 63) regions only. The protein is strongly homologous to the 7 kDa proteins of Sulfolobus acidocaldarius with the highest homology to protein 7d. Accordingly, the name of this protein from S. solfataricus was assigned as DNA-binding protein Sso7d.
Asunto(s)
Archaea/análisis , Bacterias/análisis , Proteínas de Unión al ADN/aislamiento & purificación , Secuencia de Aminoácidos , ADN de Cadena Simple/metabolismo , Microscopía Electrónica , Datos de Secuencia Molecular , Fragmentos de Péptidos/análisis , Conformación ProteicaRESUMEN
Abdominal pain for the General Practitioner (GP) is an important problem and presents as a significant challenge since the complaint emerges to the primary care provider as one of the 3 most important complaints. This paper serves as a facilitator and guide in helping the General Practitioner differentiate between the so-called normal abdominal pain versus severe abdominal pain which should be referred to a specialist. One of the most important messages the paper attempts to convey is that patients have to be seen and personally examined by the General practitioner. This is a paramount feature in establishing course of severity and outcome. Since approximately 25% of all presenting abdominal pain complaints are unclear, even to the experienced specialist, the authors attempt to direct a focused exam by means of a thorough history and physical examination and then to formulate a decision tree regarding the question of referral or continued primary care by the provider.