Role of dendrimers in advanced drug delivery and biomedical applications: a review.

AIM: Dendrimers dendritic structural design holds vast promises, predominantly for drug delivery, owing to their unique properties. Dendritic architecture is widespread topology found in nature and offers development of specific properties of chemical substances. Dendrimers are an ideal delivery vehicle candidate for open study of the effects of polymer size, charge, and composition on biologically relevant properties such as lipid bilayer interactions, cytotoxicity, bio-distribution, internalization, blood plasma retention time, and filtration. This article reviews role of dendrimers in advanced drug delivery and biomedical applications.

Microengineered cancer-on-a-chip platforms to study the metastatic microenvironment.

More than 90% of cancer-related deaths can be attributed to the occurrence of metastatic diseases. Recent studies have highlighted the importance of the multicellular, biochemical and biophysical stimuli from the tumor microenvironment during carcinogenesis, treatment failure, and metastasis. Therefore, there is a need for experimental platforms that are able to recapitulate the complex pathophysiological features of the metastatic microenvironment. Recent advancements in biomaterials, microfluidics, and tissue engineering have led to the development of living multicellular microculture systems, which are maintained in controllable microenvironments and function with organ level complexity. The applications of these "on-chip" technologies for detection, separation, characterization and three dimensional (3D) propagation of cancer cells have been extensively reviewed in previous works. In this contribution, we focus on integrative microengineered platforms that allow the study of multiple aspects of the metastatic microenvironment, including the physicochemical cues from the tumor associated stroma, the heterocellular interactions that drive trans-endothelial migration and angiogenesis, the environmental stresses that metastatic cancer cells encounter during migration, and the physicochemical gradients that direct cell motility and invasion. We discuss the application of these systems as in vitro assays to elucidate fundamental mechanisms of cancer metastasis, as well as their use as human relevant platforms for drug screening in biomimetic microenvironments. We then conclude with our commentaries on current progress and future perspectives of microengineered systems for fundamental and translational cancer research.

Ultrastrong and Flexible Hybrid Hydrogels based on Solution Self-Assembly of Chitin Nanofibers in Gelatin Methacryloyl (GelMA).

We demonstrate ultrastrong and flexible hydrogels by self-assembling chitin nanofiber in the presence of gelatin methacryloyl. We tune the mechanical properties of the hydrogel with chitin nanofiber content and show proof-of-concept applications in engineering vascular tissue.

[Conductive disorders following open-heart valvular surgery. Concerning 230 operated patients]. / Les troubles conductifs après chirurgie cardiaque valvulaire sous circulation extracorporelle. A propos de 230 malades opérés.

AIMS: Conductive disorders following open-heart valvular surgery represent serious complications that may require definitive pacemaker implantation. The natural history of these troubles is not well established thus, controversy persist concerning the timing of pacemaker implantation. In this study we identify the predictive factors of permanent conductive disorders in order to assess the optimal time of pacing. METHODS AND RESULTS: Two hundred thirty valvular replacements were done between 1993 and 2003. The mean age of our patients was 42 +/- 13.4 years. Rheumatic valvulopathies accounted for 76% of cases, with 54% of multiple valvulopathies. Twenty-two patients (9,5%) had an early postoperative conductive disorder, 9 of them (4%) were definitively implanted after a mean delay of 31.8 days. Preoperative bifascicular bloc and early installation of postoperative high-grade conduction disturbances and its persistence for more than 48 hours are significantly associated with permanent postoperative conductive disorders (respectively P = 0.04 and = 0.03). Aortic valve surgery and infective endocarditis were more frequent in the implanted group but the difference was not significant. CONCLUSION: After open-heart valvular surgery; predictive factors of definitive conductive troubles justify an earlier pacemaker implantation. This attitude may accelerate the hospital discharge and decrease the disease cost effectiveness.

[Brucella endocardititis: clinical particularities and therapeutic modalities]. / Endocardite brucellienne: particularités cliniques et modalités thérapeutiques.

Brucella infective endocarditis is an uncommon, but serious complication of brucellosis. The aortic valve is the most commonly affected cardiac valve. Due to characteristics of the infection, medical therapy alone is not sufficient in treating the disease and best results are obtained with surgery combination. We describe a case of Brucella endocarditis involving the aortic valve suspected in front of the clinical data and the results of serology, confirmed by the culture of the native valves. In association with the medical treatment, management valve replacement lead to a favorable medium-term evolution.

[Predictive value of the markers of inflammation in acute coronary syndromes]. / Valeur prédictive des marqueurs de l'inflammation au cours des syndromes coronaires aigus.

This prospective study aims to establish the association between markers of inflammation (CRP and fibrinogen) and the severity of coronary lesions in patients with acute coronary syndromes. For this purpose, Plasma CRP, fibrinogen and troponin I were measured upon admission in 143 consecutive patients presenting with an acute coronary syndrome who underwent subsequently coronarography . Mean age is 55.5+/-11.6 years. Sex Ratio is 3.61 in favour of men; 68% of our patients presented with acute myocardial infarction with ST segment elevation; 23% with an unstable angina and 9% with an acute myocardial infarction without ST segment elevation. 31 patients (24.4%) have not any significant coronary lesion. Mean CRP level in these patients is (6.82+/-8.2 mg/l) lower than that measured in patients with significant lesions (17.4+/-26.9 mg/l; p=0.02). In patients with pathologic coronarogram, we demonstrated that the mean CRP level is higher in patients heaving one or more lesion of at least 70% of diameter stenosis than that in patients with no significant lesions (21.28+/-30.45 mg/l vs 11+/-14.2 mg/l; p=0.05). The mean CRP level grows with the number of proximal and significant stenoses. (CRP level in patients with one significant stenosis: 11+/-14.2 mg/l vs 27.45+/-39.67 mg/l in patients heaving 3 lesions; p=0.02. CRP level in patients with one proximal lesion: 14.35+/-19.8 mg/l vs 50.33+/-65 mg/l in patients heaving 3 proximal lesions; p=0.007). Fibrinogen levels measured upon admission in patients having significant lesions are higher than those measured in patients with normal coronary arteries (4.7+/-1.81 mg/l vs 3.93+/-1.69 mg/l; p=0.02). Compared with that measured in patients having distal lesions, the fibrinogen level is higher in case of proximal and multiple coronary lesions. There is a significant gradual increase in fibrinogen levels with increasing of the number of proximal coronary lesions and the degree of diameter stenosis. Multivariate logistic regression analysis showed that a CRP level higher than 10 mg/l is an independent predictive factor of the presence of the presence of significant coronary lesions (p=0.006; OR = 8.62; CI=0.7 to 7.4). We conclude that high CRP and fibrinogen plasma levels are associated with extended, severe and proximal coronary lesions.

[Doppler echocardiographic study of left ventricular diastolic function in hemodialysis patients]. / Etude échocardiographique de la fonction diastolique ventriculaire gauche chez les insuffisants rénaux hémodialysés.

OBJECTIVES: The purpose of this study is to examine the diastolic dysfunction particularities in hemodialysis patients and to identify the parameters having the most discriminating power of diastolic dysfunction. METHODS: Conventional Doppler echocardiography study implies left ventricular diastolic function from Doppler transmitral flow (E/A), color M-mode flow propagation velocity (Vp) and combined indexes: ratio of peak E-wave velocity to Vp (ENp) and difference in duration of pulmonary venous and mitral flow at atrial contraction (Ap-Am). RESULTS: Left ventricular diastolic dysfunction is found in 86% of the 100 hemodialysis patients: abnormal relaxation pattern 52%, pseudo-normal pattern 21%, restrictive pattern 13%. Left ventricular hypertrophy is independent of blood pressure (eta2=3.386; p>0.06). Diastolic function pattern has no relation with duration of dialysis treatment (F=2.637, p>0.05) or left ventricular mass (F=4.298, p>0.06). We noted correlations with age for all parameters of transmitral Doppler flow (p<0.01), Vp and systolic fraction except combined indexes (p>0.05). Doppler parameters of which discriminating power is significant (p<0.001) are in deceasing order: isovolumic relaxation time, E/A, Vp, early filling deceleration time, Ap-Am, E/VP and systolic fraction. The parameter Vp discriminates normal filling from abnormal or pseudo-normal patterns. However it doesn't allow any discrimination between abnormal and pseudo-normal patterns or abnormal and restrictive patterns. Discriminating analysis classify correctly 100% of pseudo normal pattern patients with 2 variables (isovolumic relaxation time and Vp or VP with E/Vp). Factor analysis suggests that Vp characterizes normal pattern and E/A ratio and Ap-Am characterize restrictive pattern. CONCLUSION: Parameters of diastolic function discriminating value is different from one stage to another. VP characterizes normal pattern, combined indexes restrictive pattern. Vp and isovolumic relaxation time discriminates normal from pseudo-normal pattern.

[Long-term outcome of surgically treated teratology of Fallot]. / Evolution a long-terme de la tetralogie de Fallot operee.

Tetralogy of Fallot is the most common cyanotic congenital heart disease. The surgical treatment that is palliative or complete repair has allowed to transform the preview of this heart disorder. We suggests to study the long term outcome in patients undergoing surgical repair of tetralogy of Fallot, by emphasizing the quality of their lives, the complications, as well as the mortality. Ventricular arrhythmia and sudden cardiac death after repair of tetralogy of Fallot are devastating complications in adults survivors and their prediction remains difficult.

[Thoracic ectopia cordis with tetralogy of fallot]. / Ectopia cordis thoracique associe a une tetralogie de Fallot.

Ectopia cordis; very rare congenital malformation, characterized by an evisceration of the heart through a parietal defect. The thoracic localization is most frequent. We report the case of a full term baby girl without follow-up of the pregnancy, presenting a beating mass in thoracic position, expansive to the effort, covered by a translucent membrane corresponding to an ectopique position of the heart. Transthoracic echocardiography shows cardiac malformation: Fallot tetralogy. The precocious diagnosis is possible by prenatal ultrasound examination after 12th week of pregnancy. The surgical treatment remain the only hope for these neonates. It's results depends on the associated malformations and the neonatal complications especially the infections. The prognosis remains poor in spite of the progress of surgical techniques.