Regular and platform switching: bone stress analysis varying implant type

Purpose: This study aimed to evaluate stress distribution on peri‐implant bone simulating the influence of platform switching in external and internal hexagon implants using three‐dimensional finite element analysis. Materials and Methods: Four mathematical models of a central incisor supported by an implant were created: External Regular model (ER) with 5.0 mm × 11.5 mm external hexagon implant and 5.0 mm abutment (0% abutment shifting), Internal Regular model (IR) with 4.5 mm × 11.5 mm internal hexagon implant and 4.5 mm abutment (0% abutment shifting), External Switching model (ES) with 5.0 mm × 11.5 mm external hexagon implant and 4.1 mm abutment (18% abutment shifting), and Internal Switching model (IS) with 4.5 mm × 11.5 mm internal hexagon implant and 3.8 mm abutment (15% abutment shifting). The models were created by SolidWorks software. The numerical analysis was performed using ANSYS Workbench. Oblique forces (100 N) were applied to the palatal surface of the central incisor. The maximum (σ_max) and minimum (σ_min) principal stress, equivalent von Mises stress (σ_vM), and maximum principal elastic strain (ε_max) values were evaluated for the cortical and trabecular bone. Results: For cortical bone, the highest stress values (σ_max and σ_vm) (MPa) were observed in IR (87.4 and 82.3), followed by IS (83.3 and 72.4), ER (82 and 65.1), and ES (56.7 and 51.6). For ε_max, IR showed the highest stress (5.46e‐003), followed by IS (5.23e‐003), ER (5.22e‐003), and ES (3.67e‐003). For the trabecular bone, the highest stress values (σ_max) (MPa) were observed in ER (12.5), followed by IS (12), ES (11.9), and IR (4.95). For σ_vM, the highest stress values (MPa) were observed in IS (9.65), followed by ER (9.3), ES (8.61), and IR (5.62). For ε_max, ER showed the highest stress (5.5e‐003), followed by ES (5.43e‐003), IS (3.75e‐003), and IR (3.15e‐003). Conclusion: The influence of platform switching was more evident for cortical bone than for trabecular bone, mainly for the external hexagon implants. In addition, the external hexagon implants showed less stress concentration in the regular and switching platforms in comparison to the internal hexagon implants.     

Phase II study of sorafenib in patients with relapsed or refractory lymphoma

The safety and activity of the multikinase inhibitor sorafenib were investigated in patients with relapsed or refractory lymphoproliferative disorders who received sorafenib (400 mg) twice daily until disease progression or appearance of significant clinical toxicity. The primary endpoint was overall response rate (ORR). Biomarkers of sorafenib activity were analysed at baseline and during treatment. Thirty patients (median age, 61 years; range, 18-74) received a median of 4 months of therapy. Grade 3-4 toxicities included hand/foot skin reactions (20%), infections (12%), neutropenia (20%) and thrombocytopenia (14%). Two patients achieved complete remission (CR), and two achieved partial remission (PR) for an ORR of 13%. Stable disease (SD) and progressive disease (PD) was observed in 15 (50%) and 11 patients (37%), respectively. The median overall survival (OS) for all patients was 16 months. For patients who achieved CR, PR and SD, the median time to progression and OS was 5 and 24 months, respectively. Compared with patients with PD, responsive patients had significantly higher baseline levels of extracellular signal-regulated kinase phosphorylation and autophagy and presented a significant reduction of these parameters after 1 month of therapy. Sorafenib was well tolerated and had a clinical activity that warrants development of combination regimens.     

Stress amplifies lung tissue mechanics, inflammation and oxidative stress induced by chronic inflammation

ABSTRACT Background: Mechanisms linking behavioral stress and inflammation are poorly understood, mainly in distal lung tissue. Objective: We have investigated whether the forced swim stress (FS) could modulate lung tissue mechanics, iNOS, cytokines, oxidative stress activation, eosinophilic recruitment, and remodeling in guinea pigs (GP) with chronic pulmonary inflammation. Methods: The GP were exposed to ovalbumin or saline aerosols (2×/wk/4wks, OVA, and SAL). Twenty-four hours after the 4th inhalation, the GP were submitted to the FS protocol (5×/wk/2wks, SAL-S, and OVA-S). Seventy-two hours after the 7th inhalation, lung strips were cut and tissue resistance (Rt) and elastance (Et) were obtained (at baseline and after OVA and Ach challenge). Strips were submitted to histopathological evaluation. Results: The adrenals' weight, the serum cortisol, and the catecholamines were measured. There was an increase in IL-2, IL-5, IL-13, IFN-γ, iNOS, 8-iso-PGF2α, and in %Rt and %Et after Ach challenge in the SAL-S group compared to the SAL one. The OVA-S group has had an increase in %Rt and %Et after the OVA challenge, in %Et after the Ach and in IL-4, 8-iso-PGF2α, and actin compared to the OVA. Adrenal weight and cortisol serum were increased in stressed animals compared to nonstressed ones, and the catecholamines were unaltered. Conclusion & clinical relevance: Repeated stress has increased distal lung constriction, which was associated with an increase of actin, IL-4, and 8-iso-PGF2α levels. Stress has also induced an activation of iNOS, cytokines, and oxidative stress pathways.     

Gonadotrophin secretion pattern in anorchid boys from birth to pubertal age: pathophysiological aspects and diagnostic usefulness

Context The biphasic ontogeny of serum gonadotrophins observed in normal children also exists in girls with gonadal dysgenesis, although with higher levels. However, limited data exist in prepubertal boys with anorchia. Objective To investigate whether the existence of testicular tissue is required for gonadotrophin downregulation in boys. Secondarily, we analysed the prevalence of high gonadotrophins and its diagnostic value to assess the presence or absence of testes in childhood. Study design In a retrospective, semi‐longitudinal study, we compared serum gonadotrophin levels in 35 boys with anorchia aged 0–18 years, in 29 bilaterally cryptorchid boys with abdominal testes and in 236 normal boys. Results In anorchid boys, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were abnormally high in the first months after birth, then decreased progressively. LH decreased more readily than FSH and dropped to normal values in up to 70% of anorchid patients before the usual age of pubertal onset, when both gonadotrophins increased again to very high levels. In cryptorchid boys, FSH was elevated in a significantly (P < 0·0001) lower proportion of cases. Below the age of 6 years, FSH below 2 IU/l ruled out anorchia and LH above 5 IU/l confirmed anorchia with high accuracy. Between 6 and 11 years, FSH or LH levels above 5 IU/l were highly specific for the absence of testes. Conclusions The U‐shaped pattern of serum gonadotrophins observed in normal males from birth to puberty was also found in anorchid boys, but with gonadotrophin levels considerably elevated. Serum gonadotrophin levels may normalize in anorchid boys during late childhood only to rise again at puberty. The presence of testicular tissue results in restrain of gonadotrophin secretion in most patients, even if the testes are cryptorchid.     

Coronary embolism and calcified aortic valve: is there a correlation?

Coronary artery embolism is an uncommon cause of myocardial infarction. We report a case of acute ST-segment elevation myocardial infarction due to a coronary embolism that originated from a calcified aortic valve. Coronary angiography demonstrated complete occlusion of the left anterior descending coronary artery. Primary percutaneous coronary intervention was successfully performed, with aspiration of the valve tissue and complete restoration of the coronary artery blood flow. This was followed by aortic valve replacement a few days later.     

Nitric oxide boosts TLR‐4 mediated lipocalin 2 expression in chondrocytes

Lipocalin 2 (LCN2) has recently emerged as a novel adipokine involved in different processes including arthritis and chondrocyte inflammatory response. However, little is known about its activity on chondrocyte homeostasis and its regulation by nitric oxide (NO) Hence, we performed a set of experiments aimed to achieve a better understanding of this relationship. Cell vitality was tested in the ATDC5 cell line by the MTT colorimetric assay. Protein expression and gene expression was evaluated by Western blot and real time RT‐PCR, respectively. NO production (determined as nitrite accumulation) was assayed by the Griess reaction. First, we demonstrated that LCN2 decreased murine chondrocytes vitality. Next, LCN2 co‐stimulation with LPS enhanced NOS2 protein expression by murine chondrocytes. In addition, inhibition of LPS‐induced nitric oxide production by aminoguanidine, a selective NOS2 inhibitor, significantly reduced LPS‐mediated LCN2 expression. In contrast, treatment of murine chondrocytes with sodium nitroprussiate (SNP), a classic NO donor, scarcely induced LCN2 expression. Intriguingly, SNP addition to LPS‐challenged chondrocytes, treated with aminoguanidine, provoked a strong induction of LCN2 expression. Finally, murine ATDC5 cells, co‐cultured with LPS pre‐challenged macrophages, had higher LCN2 expression in comparison with murine chondrocytes co‐cultured with non pre‐challenged macrophages. In this work we have described for the first time that NO is able to exert a control on LCN2 expression, suggesting the existence of a feedback loop regulating its expression. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1046–1052, 2013