The molecular biology of distraction osteogenesis

Distraction osteogenesis has become a mainstay in bone engineering and the recent application of this technique to the membranous craniofacial skeleton has significantly improved our armamentarium for reconstructive craniomaxillofacial procedures. However, if the biomechanical, histological and ultrastructural changes associated with distraction osteogenesis have been widely described, the molecular mechanisms governing the formation of new bone in the interfragmental gap of gradually distracted bone segments remain largely unclear. Recently, our laboratory has described a rat mandibular distraction model that provides an excellent environment for deciphering the molecular mechanisms that mediate distraction osteogenesis. In this Article, we present the hypotheses and current research that have furthered our knowledge of the molecular mechanisms that govern distraction osteogenesis. Recent studies have implicated a growing number of cytokines that are intimately involved in the regulation of bone synthesis and turnover. The gene regulation of numerous cytokines (Transforming Growth Factor-B, Bone Morphogenetic Proteins, Insulin-like Growth Factor-1, Fibroblast Growth Factor-2) during distraction osteogenesis have been best characterized and will be discussed in this text. We believe that novel systems like the rat model will facilitate our understanding of the biomolecular mechanisms that mediate membranous distraction osteogenesis and will ultimately guide the development of targeted-strategies designed to accelerate bone healing.     

Evaluation of ventricular asynchronism by Doppler tissue imaging in patients with idiopathic dilated cardiomyopathy

OBJECTIVES: To study ventricular asynchronism with tissue Doppler imaging in patients with primitive dilated cardiomyopathy and narrow QRS. PATIENTS AND METHODS: We compared a group of patients with DCM and QRS < 120 ms (gr 1, n=25, 52+/-14 yrs, LVEF: 25+/-9%) with a group of normal patients (gr 2, n=16, 36+/-20 yrs). We measured the delays between the beginning of QRS and the beginnings of aortic (QA), mitral (QM), tricuspid (QT) and pulmonary (QP) flows, and of systolic (QSm) and protodiastolic (QEm) wall motion waves recorded with TDI in the basal portion of interventricular septum (IVS) and LV and RV free walls. We then calculated the differences QA-QP, QM-QT, the interparietal differences for QSm and QEm, and the maximal interparietal systolic (QSm max) and diastolic (QEm max) delays. RESULTS: QA, QP, QM and QT were significantly lengthened in group 1 patients but there were no difference between both groups for QA-QP and QM-QT. There was a trend toward a lengthening of QSm and QEm in group 1 patients. Interparietal differences of QSm and QEm were similar in both groups; however, QSm max and QEm max were significantly longer in group 1 patients than in group 2. CONCLUSION: Doppler study of patients with DCM and narrow QRS shows a lengthening of all electromechanical delays and suggests some degree of ventricular asynchronism by showing a significant increase in maximal interparietal systolic and diastolic delays.     

肺癌患者血清促血管生成素2水平及其临床意义

目的 分析不同病理分型、不同临床分期的肺癌患者中促血管生成素-2(Ang-2)的表达水平,进一步探讨该病的发病机理,为临床诊断提供依据.方法 对112例肺癌患者,16例健康体检者进行血清Ang-2检测,同时进行血清中其他相关肿瘤标志物检测.比较不同病理分型、临床分期及远处转移患者血清Ang-2的不同.结果 非小细胞肺癌患者血清Ang-2水平高于正常对照组(与鳞癌比较Sig 值为0.049,P＜0.05;与腺癌比较Sig值为0.011,P＜0.05);非小细胞肺癌Ⅲ、Ⅳ期患者血清Ang-2水平高于对照(与Ⅲ期比较Sig值为0.013,P＜0.05;与Ⅳ期比较Sig值为0.000,P＜0.001);远处转移患者血清Ang-2水平非常显著高于非远处转移者(Sig值为0.008,P＜0.01);结论 分析血清Ang-2水平对肺癌患者的临床诊断、预测转移和预后判断均有临床价值,应用Ang-2与其他肿瘤标志物联合检测可提高患者诊断阳性率.     

Stem cell evolutionary paradigm and cell engineering

Studying hematopoietic and mesenchymal stem cells for almost three decades revealed some similarities between the stem cell entity and the single-celled eukaryotes exhibiting the anaerobic/facultative aerobic metabolic features. A careful analysis of nowadays knowledge concerning the early eukaryotic evolution allowed us to reveal some analogies between stem cells in the metazoan tissues and the single-celled eukaryotes which existed during the first phase of eukaryotes evolution in mid-Proterozoic era. In fact, it is possible to trace the principle of the self-renewal back to the first eukaryotic common ancestor, the first undifferentiated nucleated cell possessing the primitive, mostly anaerobically-respiring mitochondria and a capacity to reproduction by a simple cell division “à l’identique”. Similarly, the diversification of these single-cell eukaryotes and acquiring of complex life cycle allowed/conditioned by the increase of O₂ in atmosphere (and consequently in the water environment) represents a prototype for the phenomenon of commitment/differentiation. This point of view allowed to predict the ex-vivo behavior of stem cells with respect to the O₂ availability and metabolic profile which enabled to conceive the successful protocols of stem cell expansion and ex vivo conditioning based on “respecting” this relationship between the anaerobiosis and stemness. In this review, the basic elements of this paradigm and a possible application in cell engineering were discussed.     

Adherence of Renal Transplant Recipients to Once-daily,Prolonged-Release and Twice-daily,Immediate-release Tacrolimus-based Regimens in a Real-life Setting in Sweden

Background

In this study we investigated medication adherence of kidney transplant patients (KTPs) to an immediate-release tacrolimus (IR-T) regimen and, after conversion, to a prolonged-release tacrolimus (PR-T) regimen in routine clinical practice.

Maladie cœliaque

Celiac disease is an enteropathy due to gluten intake in genetically predisposed individuals (HLA DQ2/DQ8). Celiac disease occurs in adults and children at rates approaching 1% of population in Europe and USA. Clinical features observed in celiac disease are extremely various and anaemia, oral aphthous stomatis, amenorrhea or articular symptoms may be the only presenting manifestations. Diagnosis relies on the evidence of histological villous atrophy in proximal small bowel and the presence of specific serum antibodies. Treatment relies on eviction of gluten (wheat, barley, rye) from diet. Gluten free diet allows prevention of malignant complications such as small bowel adenocarcinoma and lymphoma, and osteopenia. The main cause of resistance to gluten free diet is its poor observance. If not the case, serious complications of celiac disease, such as clonal refractory celiac sprue and intestinal T-cell lymphoma should be suspected. Current therapeutic challenges concern alternative to gluten free diet and new efficient treatments of lymphomatous complications.     

Venous oximetry: physiology and therapeutic implications

Objectives

The aims of this review are to point out the determinants of oxygen saturation of the haemoglobin of mixed venous blood (SvO₂), to specify the correlations existing between SvO₂ and central venous saturation in superior vena cava (ScvO₂), to determine and finally to locate the current place of venous oximetry in clinical practice.

Data sources

A PubMed^® database research in English and French languages published until December 2006. The keywords were mixed venous blood oxygen saturation; oxygen consumption; oxygen delivery; oxygen extraction; tissue hypoxia; central venous oxygen saturation.

Data extraction

Data in selected articles were reviewed, clinical and basic science research relevant information was extracted.

Data synthesis

The SvO₂ reflects the peripheral extraction of oxygen (O₂), O₂ delivery and consumption. Its value is related to four determinants: the O₂ consumption (VO₂), cardiac flow (CF), haemoglobin level (Hb) and O₂ saturation of the haemoglobin of arterial blood (SaO₂). ScvO₂ is more easily measurable than SvO₂. Under physiological conditions its value is 2 to 3% lower than that of SvO₂. In the critically ill patient, its value is 5% higher than that SvO₂. In most patients, changes in ScvO₂ values parallel those in SvO₂. The clinical interest of the monitoring of venous oximetry was underlined in cases of severe sepsis and septic shock, and during the perioperative period of major surgery.

Conclusion

The management of patients in critical states with therapeutic goals integrating the monitoring of venous oximetry may reduce the morbidity and mortality of patients undergoing major surgery or hospitalised in the intensive care unit.     

Enzyme optimization, mutagenesis and directed evolution

Among the different areas of biotechnology, enzyme engineering represents a growing field where major progress has been recently made. Indeed, chemical, pharmaceutical or food industries have increased needs for enzymes. This increase requires enzyme optimization in order to achieve, together or separately, greater operational stability, better specificity, increased solubility or preferential enantioselectivity. Directed and random mutagenesis, the classical methods of enzymatic engineering, have proved to be efficient in some cases, but are quite tricky. Directed evolution is a hybrid method recently developed in order to reproduce the random mechanisms of evolution in vitro. This method has now been used to optimise an increasing number of enzymes. In our research group, a directed evolution project has been initiated on a bacterial phosphotriesterase, a promising enzyme, capable of efficiently detoxifying organophosphorus nerve agents.     

Acceptability of Elderly Cancer Patients and Tolerance to COVID-19 Vaccination in the Brittany Region<br/>L’acceptabilité du Patient Âgé Porteur de Cancer et la Tolérance à la Vaccination Anti-COVID-19 dans la Région Bretagne

Context: Since January 2021, vaccination for COVID-19 has been made possible in France for people aged 75 and over. Patients suffering from a cancer disease are part of a group at risk to develop severe complications to COVID-19. Method: The « Unité de coordination en Onco-Gériatrie région Bretagne » (the Brittany This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Coordinating Unit in Onco-Geriatrics) has wished to set up an inquest about the acceptability and the tolerance to COVID-19 vaccination by old-aged patients suffering from cancer in the Brittany region. Results: The study has been carried out between May 1, 2021 and August 31, 2021 in 7 Breton centers. 50 patients have been included in the study with an average age of 84 (72-93). At the time of inclusion, 43 patients had already been vaccinated (80% having had 2 injections and 8% only one). Among them, 86% have declared they had had a very good tolerance to the first injection of the vaccine, and 90% to the second injection. 12% of the patients had not been vaccinated. Conclusion: Overall, in our study, old-aged patients suffering from cancer haven’t been reluctant to the antiCOVID-19 vaccination and have shown a very good tolerance to these vaccines. However, seen the profile of these patients and the period of inclusion, the number of patients showing a complete vaccinal outline should have been more consistent, indeed even total.

RÉSUMÉ
Contexte: Depuis le 25 janvier 2021, la vaccination de la COVID-19 a pu être réalisée en France auprès des personnes âgées de 75 ans et plus. Les patients souffrant d’une maladie cancéreuse font partie des groupes à risque de développer des complications sévères à la COVID-19. Méthode: L’Unité de Coordination en Onco-Gériatrie région Bretagne a souhaité mettre en place une enquête sur l’acceptabilité du patient âgé porteur de cancer et sur la tolérance à la vaccination anti-COVID 19 dans la région Bretagne. Résultats: L’étude a été réalisée entre le 1^er mai 2021 et le 31 août 2021 dans 7 centres bretons. 50 patients ont été inclus avec un âge médian de 84 ans (72–93). 43 patients au moment de l’inclusion avaient été vaccinés (80% ayant eu 2 injections et 8% une seule injection). Parmi eux, 86% ont déclaré avoir eu une très bonne tolérance à la première injection du vaccin et 90 % à la seconde injection. 12% des patients n’étaient pas vaccinés. Conclusion: Globalement, dans notre étude, les patients âgés porteurs de cancer ne présentaient pas de réticence à lavaccination anti-COVID19 et ont eu une très bonne tolérance à ces vaccins. Cependant, au vu du profil de ces patients et de la période d’inclusion, le nombre de patients présentant un schéma vaccinal complet aurait pu être plus conséquent.