ABSTRACT
It is important to understand the cellular and molecular events that occur at the cell-material interface of implants used for bone repair. The mechanisms involved in the initial stages of osteoblast interactions with the surface of the implant material must be decisive for cell fating surrounding them. In order to address this issue, we decided to investigate if conditioned medium for dental implants was able to modulate murine pre-osteoblast metabolism. First, we determined the concentration of titanium (Ti)-containing conditioned medium and found that it was 2-fold increased (p < 0.0001). We have reported that this conditioned medium significantly up-modulated pre-osteoblast adhesion up to 24 h (p < 0.0001). In parallel, our results showed that both phosphorylations of FAK (focal adhesion kinase) at Y397 (p < 0.0011) and Cofilin at Ser03 (p < 0.0053) were also up-modulated, as well as for Rac1 expression (p < 0.0175); both of them are involved with cell adaptation by rearranging cytoskeleton actin filaments. Thereafter, Ti-containing medium stimulated ROS (reactive oxygen species) production by pre-osteoblast cells, and it is very possible that ROS compromised PTP-1B (protein tyrosine phosphatase 1B) activation since PTP1B was down-phosphorylated (p < 0.0148). The low PTP activity guarantees the phosphorylation of FAK at Y-residue, causing better pre-osteoblast adhesion in response to Ti-containing medium. Altogether, these data indicate that ROS indirectly modulate FAK phosphorylation in response to Ti-released from dental implants. Taken the results in account, these data showed for the first time that the implanted dental device is able to dynamically affect surrounding tissues, mainly by promoting a better performance of the pre-osteoblast cells. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2968-2976, 2017.
Subject(s)
Dental Implants , Osteoblasts/drug effects , Reactive Oxygen Species/metabolism , Titanium/pharmacology , 3T3 Cells , Animals , Cell Adhesion/drug effects , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Mice , Osteoblasts/cytology , Osteoblasts/metabolism , Phosphorylation/drug effects , Signal Transduction/drug effects , Titanium/administration & dosageABSTRACT
Schistosomiasis is one of the most prevalent infectious diseases, endemic in more than 70 countries, mainly within the developing world. More than 200 million people might be infected worldwide; about 20 million of those might develop severe disease. The hepatosplenic form of schistosomiasis is the most prevalent form of chronic disease, characterised by the presence of periportal fibrosis and portal hypertension. Pulmonary hypertension is a well-recognised complication of hepatosplenic schistosomiasis. Recent prevalent studies revealed that schistosomiasis patients may develop precapillary and postcapillary forms of pulmonary hypertension, reinforcing the role of invasive haemodynamic measurements for the proper diagnosis. These studies also demonstrated that schistosomiasis associated pulmonary arterial hypertension may represent the most prevalent form of pulmonary arterial hypertension (PAH). Many aspects regarding the appropriate management of Sch-PAH patients still remain to be elucidated, as the use of specific PAH therapy. Although the ongoing control programmes that started within the 1980s have clearly improved the schistosomiasis cenario worldwide, Sch-PAH will be seen for decades after proper control is reached, strengthening the current need for comprehensive studies aiming to clarify the multiple mechanisms involved in the pathophysiology of this particular subgroup of PAH.
Subject(s)
Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/epidemiology , Schistosomiasis mansoni/diagnosis , Schistosomiasis mansoni/epidemiology , Animals , Comorbidity , Developed Countries , Developing Countries , Diagnosis, Differential , Global Health , Humans , Hypertension, Pulmonary/parasitology , Practice Guidelines as Topic , Risk Factors , Schistosoma mansoni/isolation & purification , Severity of Illness IndexABSTRACT
In recent years new therapeutic options have been developed for the management of pulmonary arterial hypertension (PAH). Sitaxsentan is an oral, once daily, highly selective endothelin A receptor antagonist that recently demonstrated a positive effect on functional capacity and haemodynamics of PAH patients. The aim of this study is to evaluate the effect of sitaxsentan in the quality of life (QOL) of PAH patients. Twenty-three patients with idiopathic PAH or PAH associated to collagen vascular diseases were evaluated at baseline and after 16 weeks of treatment with sitaxsentan 100 mg orally, once daily. 6-min walk test distance (6MWD) and QOL questionnaire (QOLQ) (SF-36) were obtained at baseline and at week 16. There was a significant improvement in functional capacity evaluated by 6MWD (472 m vs. 490 m, p = 0.03) and also in the physical component of the QOLQ (p < 0.01). Evaluating each of the domains of the SF-36 QOLQ, those more related to physical capacity presented a significant increase while the domains related to the mental component presented a trend of improvement, without reaching statistical significance. Sitaxsentan improves QOL in patients with PAH mainly through the domains related to functional capacity.
Subject(s)
Antihypertensive Agents/administration & dosage , Hypertension, Pulmonary/drug therapy , Isoxazoles/administration & dosage , Thiophenes/administration & dosage , Administration, Oral , Adult , Female , Humans , Male , Quality of LifeABSTRACT
There are few reports of pulmonary hypertension in Gaucher disease. We report a patient who showed significant clinical improvement after treatment with sildenafil.