RESUMEN
Resistance to the frontline antibiotic rifampicin constitutes a challenge to the treatment and control of tuberculosis. Here, we analyzed the mutational landscape of Mycobacterium smegmatis during long-term evolution with increasing concentrations of rifampicin, using a mutation accumulation assay combined with whole-genome sequencing. Antibiotic treatment enhanced the acquisition of mutations, doubling the genome-wide mutation rate of the wild-type cells. While antibiotic exposure led to extinction of almost all wild-type lines, the hypermutable phenotype of the ΔnucS mutant strain (noncanonical mismatch repair deficient) provided an efficient response to the antibiotic, leading to high rates of survival. This adaptative advantage resulted in the emergence of higher levels of rifampicin resistance, an accelerated acquisition of drug resistance mutations in rpoB (ß RNA polymerase), and a wider diversity of evolutionary pathways that led to drug resistance. Finally, this approach revealed a subset of adaptive genes under positive selection with rifampicin that could be associated with the development of antibiotic resistance. IMPORTANCE Rifampicin is the most important first-line antibiotic against mycobacterial infections, including tuberculosis, one of the top causes of death worldwide. Acquisition of rifampicin resistance constitutes a major global public health problem that makes the control of the disease challenging. Here, we performed an experimental evolution assay under antibiotic selection to analyze the response and adaptation of mycobacteria, leading to the acquisition of rifampicin resistance. This approach explored the total number of mutations that arose in the mycobacterial genomes under long-term rifampicin exposure, using whole-genome sequencing. Our results revealed the effect of rifampicin at a genomic level, identifying different mechanisms and multiple pathways leading to rifampicin resistance in mycobacteria. Moreover, this study detected that an increase in the rate of mutations led to enhanced levels of drug resistance and survival. In summary, all of these results could be useful to understand and prevent the emergence of drug-resistant isolates in mycobacterial infections.
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Mycobacterium tuberculosis , Tuberculosis , Humanos , Rifampin/farmacología , Tasa de Mutación , Antibacterianos/farmacología , Mutación , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Bacteriana/genética , Proteínas Bacterianas/genética , Antituberculosos/farmacologíaRESUMEN
In recent decades, an increasing number of tissue engineered bone grafts have been developed. However, expensive and laborious screenings in vivo are necessary to assess the safety and efficacy of their formulations. Rodents are the first choice for initial in vivo screens but their size limits the dimensions and number of the bone grafts that can be tested in orthotopic locations. Here, we report the development of a refined murine subcutaneous model for semi-orthotopic bone formation that allows the testing of up to four grafts per mouse one order of magnitude greater in volume than currently possible in mice. Crucially, these defects are also "critical size" and unable to heal within the timeframe of the study without intervention. The model is based on four bovine bone implants, ring-shaped, where the bone healing potential of distinct grafts can be evaluated in vivo. In this study we demonstrate that promotion and prevention of ossification can be assessed in our model. For this, we used a semi-automatic algorithm for longitudinal micro-CT image registration followed by histological analyses. Taken together, our data supports that this model is suitable as a platform for the real-time screening of bone formation, and provides the possibility to study bone resorption, osseointegration and vascularisation.
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Regeneración Ósea , Medicina Regenerativa , Animales , Materiales Biocompatibles , Bovinos , Ratones , Osteogénesis , Ingeniería de Tejidos , Andamios del TejidoRESUMEN
During skeletal development most bones are first formed as cartilage templates, which are gradually replaced by bone. If later in life those bones break, temporary cartilage structures emerge to bridge the fractured ends, guiding the regenerative process. This bone formation process, known as endochondral ossification (EO), has been widely studied for its potential to reveal factors that might be used to treat patients with large bone defects. The extracellular matrix of cartilage consists of different types of collagens, proteoglycans and a variety of non-collagenous proteins that organise the collagen fibers in complex networks. Thrombospondin-5, also known as cartilage oligomeric matrix protein (TSP-5/COMP) is abundant in cartilage, where it has been described to enhance collagen fibrillogenesis and to interact with a variety of growth factors, matrix proteins and cellular receptors. However, very little is known about the skeletal distribution of its homologue thrombospondin-4 (TSP-4). In our study, we compared the spatiotemporal expression of TSP-5 and TSP-4 during postnatal bone formation and fracture healing. Our results indicate that in both these settings, TSP-5 distributes across all layers of the transient cartilage, while the localisation of TSP-4 is restricted to the population of hypertrophic chondrocytes. Furthermore, in fractured bones we observed TSP-4 sparsely distributed in the periosteum, while TSP-5 was absent. Last, we analysed the chemoattractant effects of the two proteins on endothelial cells and bone marrow stem cells and hypothesised that, of the two thrombospondins, only TSP-4 might promote blood vessel invasion during ossification. We conclude that TSP-4 is a novel factor involved in bone formation. These findings reveal TSP-4 as an attractive candidate to be evaluated for bone tissue engineering purposes.
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Células Endoteliales , Osteogénesis , Cartílago , Proteína de la Matriz Oligomérica del Cartílago , Condrocitos , Humanos , TrombospondinasRESUMEN
The postreplicative mismatch repair (MMR) is an almost ubiquitous DNA repair essential for maintaining genome stability. It has been suggested that Mycobacteria have an alternative MMR in which NucS, an endonuclease with no structural homology to the canonical MMR proteins (MutS/MutL), is the key factor. Here, we analyze the spontaneous mutations accumulated in a neutral manner over thousands of generations by Mycobacterium smegmatis and its MMR-deficient derivative (ΔnucS). The base pair substitution rates per genome per generation are 0.004 and 0.165 for wild type and ΔnucS, respectively. By comparing the activity of different bacterial MMR pathways, we demonstrate that both MutS/L- and NucS-based systems display similar specificity and mutagenesis bias, revealing a functional evolutionary convergence. However, NucS is not able to repair indels in vivo. Our results provide an unparalleled view of how this mycobacterial system works in vivo to maintain genome stability and how it may affect Mycobacterium evolution.
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Reparación de la Incompatibilidad de ADN/genética , Mutagénesis/genética , Mutación/genética , Mycobacterium/genética , Proteínas Bacterianas/genética , Emparejamiento Base/genética , ADN Bacteriano/genética , Genes Reporteros , Genoma Bacteriano , Mutación INDEL/genética , Resistencia a la Kanamicina/genética , Tasa de Mutación , Plásmidos/genéticaRESUMEN
in tissue engineering, endochondral ossification (EO) is often replicated by chondrogenically differentiating mesenchymal stromal cells (MSCs) in vitro and achieving bone formation through in vivo implantation. The resulting marrow-containing bone constructs are promising as a treatment for bone defects. However, limited bone formation capacity has prevented them from reaching their full potential. This is further complicated since it is not fully understood how this bone formation is achieved. Acellular grafts derived from chondrogenically differentiated MSCs can initiate bone formation; however, which component within these decellularised matrices contribute to bone formation has yet to be determined. Collagen type X (COLX), a hypertrophy-associated collagen found within these constructs, is involved in matrix organisation, calcium binding and matrix vesicle compartmentalisation. However, the importance of COLX during tissue-engineered chondrogenesis and subsequent bone formation is unknown. The present study investigated the importance of COLX by shRNA-mediated gene silencing in primary MSCs. A significant knock-down of COLX disrupted the production of extracellular matrix key components and the secretion profile of chondrogenically differentiated MSCs. Following in vivo implantation, disrupted bone formation in knock-down constructs was observed. The importance of COLX was confirmed during both chondrogenic differentiation and subsequent EO in this tissue engineered setting.
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Cartílago/metabolismo , Condrogénesis , Colágeno Tipo X/metabolismo , Células Madre Mesenquimatosas/metabolismo , Osteogénesis , Animales , Cartílago/citología , Cartílago/fisiología , Células Cultivadas , Niño , Condrocitos/citología , Condrocitos/metabolismo , Colágeno Tipo X/genética , Humanos , Células Madre Mesenquimatosas/citología , Ratones , Ratones Endogámicos BALB C , Ratones DesnudosRESUMEN
BACKGROUND AND PURPOSE: We have reported that exposure to a diabetic intrauterine environment during pregnancy increases blood pressure in adult offspring, but the mechanisms involved are not completely understood. This study was designed to analyse a possible role of perivascular sympathetic and nitrergic innervation in the superior mesenteric artery (SMA) in this effect. EXPERIMENTAL APPROACH: Diabetes was induced in pregnant Wistar rats by a single injection of streptozotocin. Endothelium-denuded vascular rings from the offspring of control (O-CR) and diabetic rats (O-DR) were used. Vasomotor responses to electrical field stimulation (EFS), NA and the NO donor DEA-NO were studied. The expressions of neuronal NOS (nNOS) and phospho-nNOS (P-nNOS) and release of NA, ATP and NO were determined. Sympathetic and nitrergic nerve densities were analysed by immunofluorescence. KEY RESULTS: Blood pressure was higher in O-DR animals. EFS-induced vasoconstriction was greater in O-DR animals. This response was decreased by phentolamine more in O-DR animals than their controls. L-NAME increased EFS-induced vasoconstriction more strongly in O-DR than in O-CR segments. Vasomotor responses to NA or DEA-NO were not modified. NA, ATP and NO release was increased in segments from O-DR. nNOS expression was not modified, whereas P-nNOS expression was increased in O-DR. Sympathetic and nitrergic nerve densities were similar in both experimental groups. CONCLUSIONS AND IMPLICATIONS: The activity of sympathetic and nitrergic innervation is increased in SMA from O-DR animals. The net effect is an increase in EFS-induced contractions in these animals. These effects may contribute to the increased blood pressure observed in the offspring of diabetic rats.
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Diabetes Mellitus Experimental/fisiopatología , Arterias Mesentéricas/inervación , Acetilcolina/farmacología , Adenosina Trifosfato/metabolismo , Animales , Glucemia/análisis , Presión Sanguínea , Peso Corporal , Diabetes Mellitus Experimental/metabolismo , Estimulación Eléctrica , Femenino , Masculino , Arterias Mesentéricas/metabolismo , Arterias Mesentéricas/fisiopatología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo I/metabolismo , Embarazo , Ratas Wistar , Sodio/metabolismo , Superóxidos/metabolismo , Vasoconstricción , VasodilataciónRESUMEN
Objetivo: Determinar si la obesidad inducida por una dieta rica en grasa (HFD) está asociada con modificaciones en las funciones endotelial o neuronal, y los efectos del entrenamiento aeróbico moderado en estos cambios. Materiales y métodos: : Se utilizaron: (i) ratas control (dieta estándar); (ii) ratas alimentadas con una dieta HFD durante ocho semanas, y (iii) ratas HFD sometidas a un entrenamiento aeróbico moderado. Se analizaron las respuestas vasomotoras a acetilcolina (ACh) y estimulación eléctrica (EE), el efecto de L-NAME sobre dichas respuestas, la respuesta vasodilatadora al donante de óxido nítrico (NO) DEA-NO, las liberaciones de NO y de O2.- y la expresión de nNOS y eNOS. Resultados: La ingesta de la dieta HFD disminuyó la respuesta vasodilatadora a ACh e incrementó la respuesta vasoconstrictora a EE. El efecto del L-NAME fue menor en ambos casos en ratas HFD. Las liberaciones de NO endotelial y neuronal fueron disminuidas en ratas HFD. La liberación de O2.- solo aumentó en arterias de ratas HFD con endotelio. La vasodilatación a DEA-NO disminuyó sólo en arterias HFD con endotelio. HFD no modificó la expresión de eNOS, pero disminuyó la expresión de nNOS. Todos estos cambios fueron evitados por el entrenamiento aeróbico moderado. Conclusión: La práctica de ejercicio aeróbico moderado evitó la disfunción de la inervación nitrérgica perivascular y endotelial inducidas por una dieta HFD, evitando el desarrollo de mecanismos que favorecen la hipertensión (AU)
Objective: We investigated whether high-fat diet (HFD)-induced obesity was associated with modifications on endothelial or innervation functions, and the possible effects of aerobic exercise training on these changes. Methods: (i) Control rats (standard diet); (ii) rats fed a HFD for 8 weeks; and (iii) HFD rats submitted to an aerobic exercise training were used. Vasomotor responses to acetylcholine (ACh) and electric field stimulation (EFS), the effect of L-NAME in these responses, vasomotor responses to nitric oxide (NO) donor DEA-NO, NO and O2.- releases, and nNOS and eNOS expression were analysed. Results: : HFD decreased ACh vasodilatation and increased EFS-induced contraction. The effect of L-NAME was lower in both cases in HFD segments. Both endothelial and neuronal NO releases were decreased in HFD. O2.- release was augmented only in endothelium-intact HFD arteries. DEA-NO was decreased only in endothelium- intact segments from HFD. HFD decreased nNOS and did not modify eNOS expressions. All the modifications described were avoided after training. Conclusion: Aerobic exercise training avoided endothelial and nitrergic innervation dysfunction induced by a HFD, thus avoiding the development of mechanisms which lead to hypertension (AU)
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Animales , Masculino , Femenino , Ratas , Grasas/uso terapéutico , Grasas Insaturadas en la Dieta/uso terapéutico , Grasas de la Dieta/metabolismo , Grasas de la Dieta/uso terapéutico , Ejercicio Físico , Modelos Animales , Factores de Crecimiento Endotelial , Obesidad/complicaciones , Obesidad/dietoterapia , Obesidad/veterinaria , EndotelioRESUMEN
Anaerobic digestion (AD) technology can be employed for treating sewage sludge, livestock waste or food waste. Generally, the hydrolysis stage is the rate-limiting step of the AD processes for solid waste degradation. Therefore, physical, chemical and biological pre-treatment methods or their combination are required, in order to reduce the rate of such a limiting step. In this study, four methods (mechanical shredding, acid hydrolysis, alkaline hydrolysis and sonication) were tested to improve methane production and anaerobic biodegradability of different agro-food wastes and their mixtures. The kinetics of anaerobic degradation and methane production ofpre-treated individual wastes and selected mixtures were investigated with batch tests. Sonication at lower frequencies (37 kHz) proved to give the best results with methane productivity enhancements of over 100% in the case of pig manure and in the range of 10-47% for the other wastes assayed. Furthermore, the ultimate methane production was proportional, in all the cases, to the specific energy input applied (Es). Sonication can, thus, enhance waste digestion and the rate and quantity of biogas generated. The behaviour of the other pre-treatments under the conditions assayed is not significant. Only a slight enhancement of biogas production (around 10%) was detected for whey and waste activated sludge (WAS) after mechanical shredding. The lack of effectiveness of chemical pre-treatments (acid and alkaline hydrolysis) can be justified by the inhibition of the methanogenic process due to the presence of high concentrations of sodium (up to 8 g l(-1) in some tests). Only in the case of WAS did the acid hydrolysis considerably increase the biodegradability of the sample (79%), because in this case no inhibition by sodium took place. Some hints of a synergistic effect have been observed when co-digestion of the mixtures was performed.
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Agricultura , Industria de Alimentos , Residuos Industriales , Eliminación de Residuos/métodos , Eliminación de Residuos Líquidos/métodos , Anaerobiosis , Animales , Biodegradación Ambiental , Biocombustibles , Hidrólisis , Residuos Industriales/análisis , Estiércol , Metano/biosíntesis , Aguas del Alcantarillado , Sonicación , PorcinosRESUMEN
INTRODUCTION AND OBJECTIVES: A study is made of the clinical repercussions of occult metastases-micrometastases (MMs+)-or isolated tumour cells (ITCs+) in the lymph nodes of patients with stage IIA and IIB colon adenocarcinoma initially considered as corresponding to N0. MATERIAL AND METHODS: A retrospective study of 39 patients with stage IIA and IIB (T3-T4 N0 M0) colon adenocarcinoma, subjected to similar surgical and adjuvant chemotherapy treatment, with long and careful follow-up (minimum: 5 years, mean: 81.7 months) was performed on their previously resected lymph nodes, with the aid of new histological and immunohistochemical (cytokeratin) sections, in order to detect MMs or ITCs. Disease-free survival (DFS) and global survival (GS) in the two groups (patients with MMs+ or ITCs+ vs. patients without MMs or ITCs) were compared at 5 years based on the corresponding Kaplan-Meier survival curves, with the Breslow test. RESULTS: A total of 382 lymph nodes from the 39 patients (mean: 9.8; standard deviation: 6.09) were revised. MMs+ were detected in 2 cases and ITCs+ in 2 more cases on the Cytokeratin study. GS of the whole series at 5 years was 89.74% (35 patients alive) with a DFS at 5 years of 79.49% (31 patients free of disease), but the 2 cases with MMs+ were dead at 5 years, with high statistical differences between both groups (MMs+/MMs-) (p<0.0001). When comparing the group of MMs+/ITCs+ patients and the group of MM-/ITCs- patients, the DFS and GS times at 5 years were higher in the MMs-/ITCs- group (p=0.0692 and p=0.006 respectively). CONCLUSIONS: Although the incidence of MMs+ or ITCs+ in the examined lymph nodes was low, the presence of MMs is related to a dramatic reduction in GS and DFS at 5 years. We encourage a detailed histological study of lymph nodes resected in patients with deep penetrating colon tumours in order to assure a pN0 status (AU)
No disponible
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Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias del Colon/patología , Neoplasias del Colon/sangre , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Neoplasias del Colon/cirugía , Quimioterapia Adyuvante , Estudios de Seguimiento , Queratinas/metabolismo , Metástasis Linfática , Estadificación de Neoplasias/métodos , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
We investigated lithium-induced changes in norepinephrine (NE) catabolism. NE and its major metabolites 3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4-dihydroxyphenyl glycol (DHPG), ions such as lithium (Li(+)), magnesium (Mg(2+)), and potassium (K(+)) were measured in rat plasma and cerebral cortex using an HPLC method with electrochemical detection for amines. The results obtained with a group of rats treated by lithium chloride (2 mmol/kg/IP) were compared with a control group receiving sodium chloride (2 mmol/kg/IP). Animals were killed at different times over a period of six hours in the morning following salt administration to minimize possible chronobiological effects. There are two pathways leading to MHPG formation: way A, without DHPG, and way B, with DHPG. In plasma and cerebral cortex of lithium treated rats, way A catabolism seems to be preferential. Lithium increases Mg(2+) and K(+) plasma levels. These results suggest that lithium may increase inactivation of NE and decrease NE available for adrenergic receptors.
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Corteza Cerebral/metabolismo , Cloruro de Litio/farmacología , Metoxihidroxifenilglicol/análogos & derivados , Modelos Biológicos , Norepinefrina/metabolismo , Animales , Área Bajo la Curva , Cromatografía Líquida de Alta Presión , Electroquímica , Femenino , Litio/sangre , Litio/metabolismo , Magnesio/sangre , Magnesio/metabolismo , Metoxihidroxifenilglicol/sangre , Metoxihidroxifenilglicol/metabolismo , Potasio/sangre , Potasio/metabolismo , Ratas , Ratas Wistar , Cloruro de Sodio , EspectrofotometríaRESUMEN
Propósito: describir el tratamiento de una entidad clínica poco frecuente de curso clínico variable. Material y método: se presenta el caso de un paciente con carcinomatosis peritoneal mucinosa, varianteintermedia. Resultados y conclusiones: una cirugía de citoreducción adecuada, seguida de quimioterapia conCDDP Intraperitoneal (IP) y 5FU ev, puede lograr una larga supervivencia en pacientes afectos de carcinomatosisperitoneal, con buena tolerancia al tratamiento
Purpose: To describe the treatment of a slightly frequent clinical entity of variable clinical course. Material and methods: We present the case of a patient with mucinous peritoneal carcinomatosis,intermediate variant. Results and conclusion: A suitable cytoreductive surgery, followed by chemotherapy withintraperitoneal CDDP and intravenous 5-FU, can achieve a long survival of patients with peritonealcarcinomatosis, with good tolerance for the treatment
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Masculino , Anciano , Humanos , Cisplatino/administración & dosificación , Seudomixoma Peritoneal/terapia , Neoplasias Peritoneales/terapia , Adenocarcinoma Mucinoso/patologíaRESUMEN
A pleomorphic undifferentiated tumor primarily located in the retroperitoneum with a phenotype compatible with an extraosseous Ewing tumor/peripheral primitive neuroectodermal tumor (ET/pPNET) pattern and unusual molecular features is described. Immunohistochemically, HBA-71 (CD99/mic2) and several neural markers were intensively expressed together with scattered cells expressing carcinoembryonic antigen (CEA). Short-term culture showed biphasic neuroblastic and epithelioid cell populations, with the latter expressing germ cell markers (CEA, alpha-fetoprotein, and the beta-subunit of chorionic gonadotrophin). Conventional cytogenetics displayed several chromosomic rearrangements, especially a complex translocation t(17,2,22,13) (q21::q11-->q33::q12-->q13::q14). These structural abnormalities were confirmed using fluorescence in situ hybridization analysis. Molecular studies revealed EWS-FEV fusion transcripts (exon 7 of the EWS gene and exon 2 of the FEV gene). In addition, a new p53 mutation not previously reported in ET/pPNET involving exon 5 codon 138: GCC to GAC (Ala/Asp) was detected. In our case, we emphasize the presence of atypical features not only from the phenotypic point of view but also at the genetic level as well as the value of detecting such markers in the differential diagnosis with other abdominal pleomorphic tumors.
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Tumores Neuroectodérmicos Primitivos/patología , Neoplasias Retroperitoneales/patología , Sarcoma de Ewing/patología , Neoplasias de los Tejidos Blandos/patología , Adulto , Biomarcadores de Tumor/análisis , Bandeo Cromosómico , Cromosomas Humanos Par 11 , Cromosomas Humanos Par 22 , ADN de Neoplasias/análisis , Resultado Fatal , Reordenamiento Génico , Genes p53 , Humanos , Cariotipificación , Masculino , Mutación , Neoplasias Primarias Secundarias , Tumores Neuroectodérmicos Primitivos/química , Tumores Neuroectodérmicos Primitivos/genética , Proteínas de Fusión Oncogénica/genética , Neoplasias Retroperitoneales/química , Neoplasias Retroperitoneales/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sarcoma de Ewing/química , Sarcoma de Ewing/genética , Neoplasias de los Tejidos Blandos/química , Neoplasias de los Tejidos Blandos/genética , Translocación Genética , Células Tumorales CultivadasRESUMEN
Chronic patellar tendinosis or "jumper's knee" is a frequent source of persistent and often recurrent anterior knee pain in active, young people. Seventeen pathologic specimens retrieved during surgery for jumper's knee were evaluated by means of immunohistochemical (S-100) analysis. The patellar tendon-bone junction and the Hoffa fat pad adjacent to the inferior pole of the patella are structures that have a nerve supply that can be a potential source of nociceptive output resulting in the perception of pain at any given moment. In this study, pathologic neural changes also were observed. In eight cases, free nerve endings showed a histologic pattern of "nerve sprouting" in the patellar tendon-bone junction. Vascular innervation was seen in seven cases. S-100 positive fibers were observed within the muscular layer of medium and small arteries. These findings show an increase in vascular innervation. Lastly, neuromatous changes were observed in four cases, demonstrating a clear relationship with pain. These observations provide a neuroanatomic basis for pain in active, young patients with jumper's knee.
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Neuroanatomía , Dolor/patología , Rótula/lesiones , Rótula/patología , Traumatismos de los Tendones/patología , Adulto , Traumatismos en Atletas/diagnóstico , Enfermedad Crónica , Femenino , Humanos , Inmunohistoquímica , Traumatismos de la Rodilla/diagnóstico , Traumatismos de la Rodilla/patología , Masculino , Fibras Nerviosas Mielínicas/patología , Dolor/diagnóstico , Rótula/inervación , Traumatismos de los Tendones/diagnóstico , Tendones/inervaciónRESUMEN
We studied 7 samples of lateral retinaculae excised at the time of surgical realignments. They were obtained from patients with isolated symptomatic patellofemoral malalignment resistant to conservative treatment and were evaluated with immunohistochemistry and immunoblotting. We found that neural growth factor is higher in patients with pain than in those with instability as the main symptom. Neural growth factor is related to neural proliferation in vessels and perivascular tissue and to the release of neuroceptive transmitters, such as substance P. We postulate that both mechanisms are involved in the pathogenesis of pain in isolated symptomatic patellofemoral malalignment.
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Fémur/patología , Inestabilidad de la Articulación/patología , Articulación de la Rodilla/patología , Factores de Crecimiento Nervioso/análisis , Dolor/patología , Rótula/patología , Adolescente , Adulto , Femenino , Fémur/química , Fémur/cirugía , Regulación de la Expresión Génica , Humanos , Immunoblotting , Inmunohistoquímica , Inestabilidad de la Articulación/etiología , Inestabilidad de la Articulación/metabolismo , Articulación de la Rodilla/química , Articulación de la Rodilla/cirugía , Dolor/etiología , Dolor/metabolismo , Rótula/química , Rótula/cirugíaRESUMEN
We evaluated 13 lateral retinacula excised at the time of Insall proximal realignments or isolated lateral retinacular releases performed in patients with isolated symptomatic patellofemoral malalignment recalcitrant to nonoperative treatment. Evaluation was performed by means of conventional histologic and immunohistochemical analysis for neural markers (S-100 protein, neurofilament protein, substance P, and neural growth factor). The observations reported here provide a neuroanatomic basis for anterior knee pain syndrome in active young patients with isolated symptomatic patellofemoral malalignment and support the clinical observation that the lateral retinaculum may have a key role in the origin of this pain as a result of increased neural growth factor production, which induces proliferation of nociceptive axons, mainly in a perivascular location.
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Biomarcadores/análisis , Articulación de la Rodilla/inervación , Articulación de la Rodilla/patología , Proteínas del Tejido Nervioso/análisis , Dolor/fisiopatología , Rótula/anomalías , Adolescente , Adulto , Femenino , Humanos , Inmunohistoquímica , Articulación de la Rodilla/anatomía & histología , Masculino , SíndromeRESUMEN
Although it is universally accepted that patellofemoral malalignment is the main cause of anterior knee pain and functional patellar instability in the active young, the question remains to be answered: what is the mechanism whereby patellofemoral malalignment produces pain and instability? Currently, there are two theories to explain the origin of pain and instability in patients with patellofemoral malalignment: the neural theory and the mechanical theory. Both theories are not exclusive, but complementary. We believe it is the neural factor that precipitates the symptoms in patients with certain mechanical anomalies who also subject the knee to overuse.
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Artralgia/etiología , Inestabilidad de la Articulación/etiología , Traumatismos de la Rodilla/diagnóstico , Articulación de la Rodilla/patología , Adolescente , Adulto , Artralgia/patología , Artralgia/fisiopatología , Femenino , Fémur/diagnóstico por imagen , Fémur/fisiopatología , Humanos , Inestabilidad de la Articulación/patología , Inestabilidad de la Articulación/fisiopatología , Traumatismos de la Rodilla/complicaciones , Traumatismos de la Rodilla/fisiopatología , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/fisiopatología , Masculino , Rótula/diagnóstico por imagen , Rótula/fisiopatología , Pronóstico , Radiografía , Rango del Movimiento Articular , Índice de Severidad de la Enfermedad , DeportesRESUMEN
Patellar tendon donor defect (PTDD) healing after patellar tendon autograft (PTA), was evaluated in 12 lambs (24 knees), by means of conventional histology, immunohistochemistry and image analysis. The results of this study indicate that the PTDD is replaced by a tissue that does not assume the histological characteristics of a normal patellar tendon. Both the Hoffa fat pad (HFP) and the paratenon play an important role in the healing process, although qualitative and quantitative chronological differences were found, which supports the concept of a "two-time process". The HFP initiates the repair process, and is the main active proliferative tissue compartment during the first week. Once the process is established, the paratenon and, in particular, its synovial lining, starts proliferative activity and virtually substitutes that of the HFP, which rapidly loses activity in a few days. Moreover, donor-site morbidity after PTA could be the result of histological changes in the patellar tendon and environs in only a few cases. We have found inflammatory and neural changes in the refilled PTDD that could explain the anterior knee pain after PTA. Likewise, we have observed loss of Golgi corpuscles in the refilled PTDD, which could lead to proprioceptive loss after ACL reconstruction with PTA. Finally, we have observed shrinkage of the PTDD scar that could contribute to the etiopathogenia of a patella infera.