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Selective Posterior Epiphysiodesis of the Triradiate Cartilage of the Acetabulum: Preliminary Results of an Experimental Study in Rabbits  [PDF]
Bibiana Dello Russo
Open Journal of Orthopedics (OJO) , 2016, DOI: 10.4236/ojo.2016.68032
Abstract: Background: Residual acetabular dysplasia is one of the main complications of developmental dysplasia of the hip (DDH). Without treatment, over time degenerative osteoarthritis of the joint will develop, inexorably leading to the need for joint replacement. Acetabular and/or femoral osteotomies do not avoid the appearance of osteoarthritis in a significant number of patients. The purpose of this study was to assess the possibility of provoking changes in the morphology of the acetabulum through selective epiphysiodesis of the extra-articular portion of the ilioischial arm of the triradiate cartilage, using a percutaneous cannulated screw with the guidance of an imaging intensifier in an experimental model in rabbits. Methods: In a pilot study, 3-week-old New Zealand rabbits (n = 20) were submitted to unilateral surgery of the hip while the contralateral hip of the same group was used as a control. Posterior epiphysiodesis to the triradiate cartilage of the acetabulum was performed by placement of a cannulated screw. The rabbits were followed-up until 18 weeks of life. Radiographic measurements of the hips were performed immediately postoperatively and at 12 weeks of life and before the rabbits were sacrificed at week 18. Three-dimensional computed tomography (3D-CT) scans were performed. Non-parametric tests for paired samples and the Wilcoxon test were used to compare the differences between group 1 and group 2. A p < 0.05 was considered significant. Results: The non-intervened hips showed that, when the rabbit matured, the acetabulum lost concavity and depth. When comparing the median differences of the angles evaluated at 12 weeks between groups, a statistically significant difference was found in all radiographic measurements: an increase in Wiberg’s angle but a decrease in acetabular index, acetabular angle of Sharp, acetabular depth index, and acetabular anteversion. Evaluating the operated hips at 12 and 18 weeks (three months after having removed the screw) using 3D-CT, we observed a rebound effect in the correction confirming that the effect obtained through selective epiphysiodesis did not cause the definitive closure of the cartilage. Conclusions: Selective growth arrest of the ilioischial arm of the triradiate cartilage (posterior epiphysiodesis) can alter growth and change the shape of the acetabulum in rabbits. A rebound effect was observed when the screw was removed, confirming that the technique did not provoke definitive closure of the physis. Level of evidence: Level-2, therapeutic study.
Tratamiento de las lesiones secuelares del extremo distal de la articulación radiocubital distal
Dello Russo,Bibiana; Dogliotti,Pedrio; Miscione,Horacio;
Revista de la Asociaci?3n Argentina de Ortopedia y Traumatolog?-a , 2009,
Abstract: background: distal radius fractures associated with ulnar ligament or distal epiphysial injuries are less frequent in skeletally immature patients. underestimation of injury mechanisms leads to conservative treatment for this type of fracture which results in unsatisfactory reductions and loss of range of motion. methods: between january 2000 and march 2008 ten cases were studied whose treatment involved joint reconstruction. mean age was 11.9 years. we analyzed the fracture mechanisms, time to diagnosis, definitive reduction treatment, and the number of previous surgical operations. results: mean follow-up until patients' skeletal maturity was 3.4 years. mean surgeries prior to definitive treatment was 2.1; varying from attempts at closed reductions under anesthesia to percutaneous pinning in most of the cases. 87% of the patients improved their range of motion after the definitive surgery, as noted in the latest follow-up. conclusions: this fracture pattern is generally underestimated when evaluating the treatment to be employed in children; in this type of injuries reduction should be surgical in order to achieve an adequate alignment. parents should know this method, its evolution and the possible subsequent surgeries to reestablish the joint axes and the adequate length of the wrist bones.
Prevention of Femoral Head Deformity after Ischemic Necrosis Using Ibandronate Acid and Growth Factor in Immature Pigs  [PDF]
Bibiana Dello Russo, Eduardo Luis Baroni, Nicolas Saravia, Valeria Amelong, Fabiana Lubiniecky, Marcelo Asprea, Gustavo Williams, Susana Rodriguez
Surgical Science (SS) , 2012, DOI: 10.4236/ss.2012.34037
Abstract: Background: Femoral head deformity is the most severe sequela of ischemic necrosis in skeletally immature patients. Development of severe deformity shortens useful survival time of the joint due to the appearance of early degenerative changes. Preservation of the trabecular architecture through inhibition of osteoclastic bone resorption may minimize the development of the deformity in an animal model of ischemic necrosis of the femoral head. Aims: To determine if a highly potent antiabsorptive agent, ibandronate, would inhibit bone resorption during necrotic femoral head repair to avoid subsequent flattening and deformity, to determine if the use of platelet-rich plasma stimulates bone repair and neovascularization of the damaged femoral head, and to evaluate if the combination of both therapies can preserve the femoral head while stimulating new bone formation in an animal model of ischemic necrosis. Methods: Ischemic necrosis of the femoral head was induced by surgical ligature of the circumflex vessels in 10 Landrace pigs. The animals were divided into four different groups and were administered ibandronate acid, platelet-rich plasma, or both. The contralateral, untreated femoral heads with surgical ligature of the circumflex vessels served as the control group. All animals were killed three months after surgery and the femoral head was evaluated both radiographically and histologically. The femur length was measured on radiographs and compared among the groups.Results: Final femoral length was significantly longer in the group treated with a combination of both therapies (platelet-rich plasma-ibandronate acid) compared to the others groups, with a significant difference between groups. The histological findings showed increased osteoblastic activity and thickened trabiculae, a higher rate of neovascularization, and focal hyperplasia greater bone resorption and neovascularization. Only slight changes (femoral length) were observed in the animals that received platelet-rich plasma in situ favoring revascularization that was, however, only seen in the first months of administration. Conclusions: Radiographic and histological studies showed that a combination of both therapies (platelet-rich plasma and ibandronate acid) preserved the trabecular architecture and prevented femoral head deformity in the early phase of ischemic necrosis repair in immature pigs, coinciding with reports by other authors. Clinical Relevance: These findings support the concept that a combination of antiresorptive and anabolic agents can significantly improve bone healing and
The mTOR kinase inhibitor rapamycin decreases iNOS mRNA stability in astrocytes
Lucia Lisi, Pierluigi Navarra, Douglas L Feinstein, Cinzia Dello Russo
Journal of Neuroinflammation , 2011, DOI: 10.1186/1742-2094-8-1
Abstract: Primary cultures of rat cortical astrocytes were activated with different proinflammatory stimuli, namely a mixture of cytokines (TNFα, IFNγ, and IL-1β) or by LPS plus IFNγ. Rapamycin was used at nM concentrations to block mTOR activity and under these conditions we measured its effects on the iNOS promoter, mRNA and protein levels. Functional experiments to evaluate iNOS activity were also included.In this experimental paradigm mTOR activation did not significantly affect astrocyte iNOS activity, but mTOR pathway was involved in the regulation of iNOS expression. Rapamycin did not display any significant effects under basal conditions, on either iNOS activity or its expression. However, the drug significantly increased iNOS mRNA levels after 4 h incubation in presence of pro-inflammatory stimuli. This stimulatory effect was transient, since no differences in either iNOS mRNA or protein levels were detected after 24 h. Interestingly, reduced levels of iNOS mRNA were detected after 48 hours, suggesting that rapamycin can modify iNOS mRNA stability. In this regard, we found that rapamycin significantly reduced the half-life of iNOS mRNA, from 4 h to 50 min when cells were co-incubated with cytokine mixture and 10 nM rapamycin. Similarly, rapamycin induced a significant up-regulation of tristetraprolin (TTP), a protein involved in the regulation of iNOS mRNA stability.The present findings show that mTOR controls the rate of iNOS mRNA degradation in astrocytes. Together with the marked anti-inflammatory effects that we previously observed in microglial cells, these data suggest possible beneficial effects of mTOR inhibitors in the treatment of inflammatory-based CNS pathologies.Astrocyte activation has been implicated in the pathogenesis of several neurological conditions, such as neurodegenerative diseases, infections, trauma, and ischemia. Reactive astrocytes are capable of producing a variety of pro-inflammatory mediators, including interleukin-6 (IL-6), IL-1β, tumor
Manifold benefits of choosing a minimally fluoroscopic catheter ablation approach
Michela Casella,Antonio Dello Russo,Gaetano Fassini,Daniele Andreini
World Journal of Cardiology , 2013, DOI: 10.4330/wjc.v5.i2.8
Abstract: We report the case of a 14-year-old boy with ventricular preexcitation. A standard, fluoroscopy guided, ablation procedure was successfully performed in a postero-midseptal region with a total fluoroscopy time of about 45 min (2430 cGy.cm2). A few hours after the procedure, preexcitation reappeared. A second ablation procedure was scheduled using the EnSite NavX mapping system. During mapping along the tricuspid groove, preexcitation suddenly disappeared due to mechanical “bumping” of the accessory pathway and it did not recover over the next 30 min. As per our routine practice, the phase of geometry reconstruction has been continuously recorded by the system; thus, an off-line analysis allowed to pinpoint the site of earliest activation and the site of mechanical bumping, where radiofrequency obtained the accessory pathway ablation. The second procedure was performed without using fluoroscopy at all. Thanks to the geometry reconstruction, the procedure was completely successful thus avoiding a further rehospitalization.
Rate-Control or Rhythm-Contol: Where do we stand?
Testa L,Trotta G,Dello Russo A,Casella M
Indian Pacing and Electrophysiology Journal , 2005,
Abstract: Atrial fibrillation is the most common sustained rhythm disturbance and its prevalence is increasing worldwide due to the progressive aging of the population. Current guidelines clearly depict the gold standard management of acute symptomatic atrial fibrillation but the best-long term approach for first or recurrent atrial fibrillation is still debated with regard to quality of life, risk of new hospitalizations, and possible disabling complications, such as thromboembolic stroke, major bleeds and death. Some authors propose that regaining sinus rhythm in all cases, thus re-establishing a physiologic cardiac function not requiring a prolonged antithrombotic therapy, avoids the threat of intracranial or extracranial haemorrhages due to Vitamin K antagonists or aspirin. On the contrary, advocates of a rate control approach with an accurate antithrombotic prophylaxis propose that such a strategy may avoid the risk of cardiovascular and non cardiovascular side effects related to antiarrhythmic drugs. This review aims to explore the state of our knowledge in order to summarize evidences and issues that need to be furthermore clarified.
Baseline NT-Pro-BNP Levels and Arrhythmia Recurrence in Outpatients Undergoing Elective Cardioversion of Persistent Atrial Fibrillation: A Survival Analysis
Tommaso Sanna,Andrea Sonaglion,Maurizio Pieroni,Antonio Dello Russo
Indian Pacing and Electrophysiology Journal , 2009,
Abstract: Background: Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Elective electrical cardioversion is often performed in patients with persistent AF to attempt sinus rhythm (SR) restoration. However, AF recurrences are frequent after successful cardioversion and several predictors have been identified. Aim of the study: The present study was designed to prospectively analyse the correlation between NT-pro-BNP levels and AF recurrence in consecutive patients referred for electrical cardioversion of persistent atrial fibrillation. Results: Forty consecutive patients referred for elective cardioversion of AF were enrolled in the study. Cardioversion restored sinus rhythm in 34/40 patients but 2 of them presented an early recurrence of AF before discharge. Patients were then followed for 6 months to assess AF recurrence. Cox regression analysis was performed using the parameters found predictive on univariate survival analysis (NT-pro-BNP quartiles, beta-blockers). The only independent predictor of AF recurrence on Cox-regression analysis was a level of NT-pro-BNP in the fourth quartile (HR 3.21 95%CI 1.26-8.14, p=0.014). On receiver operating curve (ROC) analysis, NT-pro-BNP levels above 1707 pg/ml had a specificity of 92% (and a sensitivity of 36%) in predicting atrial fibrillation recurrence by 6 months. Conclusions: Baseline NT-pro-BNP levels are an independent predictor of AF recurrence at 6 months follow-up in candidates for elective direct current cardioversion.
Inhibition of microglial inflammatory responses by norepinephrine: effects on nitric oxide and interleukin-1β production
Cinzia Dello Russo, Anne I Boullerne, Vitaliy Gavrilyuk, Douglas L Feinstein
Journal of Neuroinflammation , 2004, DOI: 10.1186/1742-2094-1-9
Abstract: Rat cortical microglia were stimulated with bacterial lipopolysaccharide (LPS) to induce NOS2 expression (assessed by nitrite and nitrate accumulation, NO production, and NOS2 mRNA levels) and IL-1β release (assessed by ELISA). Effects of NE were examined by co-incubating cells with different concentrations of NE, adrenergic receptor agonists and antagonists, cAMP analogs, and protein kinase (PK) A and adenylate cyclase (AC) inhibitors. Effects on the NFκB:IκB pathway were examined by using selective a NFκB inhibitor and measuring IκBα protein levels by western blots. A role for IL-1β in NOS2 induction was tested by examining effects of caspase-1 inhibitors and using caspase-1 deficient cells.LPS caused a time-dependent increase in NOS2 mRNA levels and NO production; which was blocked by a selective NFκB inhibitor. NE dose-dependently reduced NOS2 expression and NO generation, via activation of β2-adrenergic receptors (β2-ARs), and reduced loss of inhibitory IkBα protein. NE effects were replicated by dibutyryl-cyclic AMP. However, co-incubation with either PKA or AC inhibitors did not reverse suppressive effects of NE, but instead reduced nitrite production. A role for IL-1β was suggested since NE potently blocked microglial IL-1β production. However, incubation with a caspase-1 inhibitor, which reduced IL-1β levels, had no effect on NO production; incubation with IL-receptor antagonist had biphasic effects on nitrite production; and NE inhibited nitrite production in caspase-1 deficient microglia.NE reduces microglial NOS2 expression and IL-1β production, however IL-1β does not play a critical role in NOS2 induction nor in mediating NE suppressive effects. Changes in magnitude or kinetics of cAMP may modulate NOS2 induction as well as suppression by NE. These results suggest that dysregulation of the central cathecolaminergic system may contribute to detrimental inflammatory responses and brain damage in neurological disease or trauma.Microglial activation includi
Proinflammatory-activated trigeminal satellite cells promote neuronal sensitization: relevance for migraine pathology
Alessandro Capuano, Alice De Corato, Lucia Lisi, Giuseppe Tringali, Pierluigi Navarra, Cinzia Dello Russo
Molecular Pain , 2009, DOI: 10.1186/1744-8069-5-43
Abstract: Primary cultures of rat trigeminal satellite cells isolated from neuronal cultures were characterized in vitro. Cyclooxygenase (COX) expression and activity were taken as a marker of glial pro-inflammatory activation. Most of the experiments were carried out to characterize satellite cell responses to the two different pro-inflammatory stimuli. Subsequently, medium harvested from activated satellite cells was used to test possible modulatory effects of glial factors on trigeminal neuronal activity. IL-1β and the NO donor diethylenetriamine/nitric oxide (DETA/NO) elevated PGE2 release by satellite cells. The stimulatory effect of IL-1β was mediated mainly by upregulation of the inducible form of COX enzyme (COX2), while NO increased the constitutive COX activity. Regardless of the activator used, it is relevant that short exposures of trigeminal satellite cells to both activators induced modifications within the cells which led to significant PGE2 production after removal of the pro-inflammatory stimuli. This effect allowed us to harvest medium from activated satellite cells (so-called 'conditioned medium') that did not contain any stimulus, and thus test the effects of glial factors on neuronal activation. Conditioned medium from satellite cells activated by either IL-1β or NO augmented the evoked release of CGRP by trigeminal neurons.These findings indicate that satellite cells contribute to migraine-related neurochemical events and are induced to do so by autocrine/paracrine stimuli (such as IL-1β and NO). The responsiveness of IL-1β to CGRP creates the potential for a positive feedback loop and, thus, a plurality of targets for therapeutic intervention in migraine.Migraine is a complex, chronic, painful, neurovascular disorder characterized by episodic activation of the trigeminal system; in particular, trigeminal ganglia play a pivotal role in initiating and maintaining pain [1,2]. Cell bodies of trigeminal neurons extend their axonal projections to the brainste
The anti-inflammatory effects of dimethyl fumarate in astrocytes involve glutathione and haem oxygenase-1
Shao Xia Lin,Lucia Lisi,Cinzia Dello Russo,Paul E Polak
ASN Neuro , 2011, DOI: 10.1042/an20100033
Abstract: DMF (dimethyl fumarate) exerts anti-inflammatory and pro-metabolic effects in a variety of cell types, and a formulation (BG-12) is being evaluated for monotherapy in multiple sclerosis patients. DMF modifies glutathione (GSH) levels that can induce expression of the anti-inflammatory protein HO-1 (haem oxygenase-1). In primary astrocytes and C6 glioma cells, BG-12 dose-dependently suppressed nitrite production induced by either LI [LPS (lipopolysaccharide) at 1 μg/ml plus IFNγ (interferon γ) at 20 units/ml] or a mixture of pro-inflammatory cytokines, with greater efficacy in C6 cells. BG-12 reduced NOS2 (nitric oxide synthase 2) mRNA levels and activation of a NOS2 promoter, reduced nuclear levels of NF-κB (nuclear factor κB) p65 subunit and attenuated loss of IκBα (inhibitory κBα) in both cell types, although with greater effects in astrocytes. In astrocytes, LI decreased mRNA levels for GSHr (GSH reductase) and GCL (c-glutamylcysteine synthetase), and slightly suppressed GSHs (GSH synthetase) mRNAs. Co-treatment with BG-12 prevented those decreased and increased levels above control values. In contrast, LI reduced GSHp (GSH peroxidase) and GCL in C6 cells, and BG-12 had no effect on those levels. BG-12 increased nuclear levels of Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2), an inducer of GSH-related enzymes, in astrocytes but not C6 cells. In astrocytes, GSH was decreased by BG-12 at 2 h and increased at 24 h. Prior depletion of GSH using buthionine-sulfoximine increased the ability of BG-12 to reduce nitrites. In astrocytes, BG-12 increased HO-1 mRNA levels and effects on nitrite levels were blocked by an HO-1 inhibitor. These results demonstrate that BG-12 suppresses inflammatory activation in astrocytes and C6 glioma cells, but with distinct mechanisms, different dependence on GSH and different effects on transcription factor activation.
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