Particulate endocytosis mediates biological responses of human mesenchymal stem cells to titanium wear debris.

Continual loading and articulation cycles undergone by metallic (e.g., titanium) alloy arthroplasty prostheses lead to liberation of a large number of metallic debris particulates, which have long been implicated as a primary cause of periprosthetic osteolysis and postarthroplasty aseptic implant loosening. Long-term stability of total joint replacement prostheses relies on proper integration between implant biomaterial and osseous tissue, and factors that interfere with this integration are likely to cause osteolysis. Because multipotent mesenchymal stem cells (MSCs) located adjacent to the implant have an osteoprogenitor function and are critical contributors to osseous tissue integrity, when their functions or activities are compromised, osteolysis will most likely occur. To date, it is not certain or sufficiently confirmed whether MSCs endocytose titanium particles, and if so, whether particulate endocytosis has any effect on cellular responses to wear debris. This study seeks to clarify the phenomenon of titanium endocytosis by human MSCs (hMSCs), and investigates the influence of endocytosis on their activities. hMSCs incubated with commercially pure titanium particles exhibited internalized particles, as observed by scanning electron microscopy and confocal laser scanning microscopy, with time-dependent reduction in the number of extracellular particles. Particulate endocytosis was associated with reduced rates of cellular proliferation and cell-substrate adhesion, suppressed osteogenic differentiation, and increased rate of apoptosis. These cellular effects of exposure to titanium particles were reduced when endocytosis was inhibited by treatment with cytochalasin D, and no significant effect was seen when hMSCs were treated only with conditioned medium obtained from particulate-treated cells. These findings strongly suggest that the biological responses of hMSCs to wear debris are triggered primarily by the direct endocytosis of titanium particulates, and not mediated by secreted soluble factors. In this manner, therapeutical approaches that suppress particle endocytosis could reduce the bioreactivity of hMSCs to particulates, and enhance long-term orthopedic implant prognosis by minimizing wear-debris periprosthethic osteolysis.     

Operationsrisiko nach neoadjuvanter Therapie gastrointestinaler Karzinome

Zusammenfassung Viele gastrointestinale Tumoren werden im Rahmen multimodaler Therapiekonzepte behandelt. Für den Chirurgen ist die neoadjuvante, präoperative Behandlung von besonderem Interesse, da sie durch therapiebedingte Nebenwirkungen und Komplikationen zu einer Beeinflussung des postoperativen Verlaufs führen kann. Die neoadjuvante Radiochemotherapie ist fester Bestandteil der Therapie beim primären T4-Rektumkarzinom, beim Rektumkarzinomrezidiv und bei tief sitzenden primären Rektumkarzinomen. Durch Erhöhung der R0-Resektionsrate können die lokale Tumorkontrolle verbessert und die Überlebenszeit verlängert werden. Die postoperative Komplikationsrate ist dabei nicht wesentlich erhöht. In der Behandlung des primär resektablen Ösophaguskarzinoms deutet sich ein Vorteil der neoadjuvanten Radiochemotherapie im Vergleich zur alleinigen Chirurgie an. Beim lokal fortgeschrittenen Ösophaguskarzinom bietet die präoperative Radiochemotherapie häufig die einzige Chance zur Resektion, jedoch mit einer deutlich erhöhten postoperativen Morbidität und Mortalität. Die Wirksamkeit und Sicherheit einer neoadjuvanten Chemo- oder kombinierten Radiochemotherapie beim fortgeschrittenen Magenkarzinom wird derzeit im Rahmen von Studienprotokollen untersucht.     

A Survey of Plants Used as Wild Vegetables in Four Districts of Botswana

A survey of plants used as wild vegetables was conducted in four districts of Botswana in August and September 2005. The objective was to determine which wild plants were used as vegetables in the study area, and to document their cooking and preservation methods. Fourteen species representing seven families were mentioned as wild vegetables. In addition, six species from four families had other uses in traditional medicine. The implications of the documented processing methods on the retention of nutrients in the vegetables are discussed.     

BCR-ABL activity and its response to drugs can be determined in CD34+ CML stem cells by CrkL phosphorylation status using flow cytometry.

In chronic myeloid leukaemia, CD34(+) stem/progenitor cells appear resistant to imatinib mesylate (IM) in vitro and in vivo. To investigate the underlying mechanism(s) of IM resistance, it is essential to quantify Bcr-Abl kinase status at the stem cell level. We developed a flow cytometry method to measure CrkL phosphorylation (P-CrkL) in samples with <10(4) cells. The method was first validated in wild-type (K562) and mutant (BAF3) BCR-ABL(+) as well as BCR-ABL(-) (HL60) cell lines. In response to increasing IM concentration, there was a linear reduction in P-CrkL, which was Bcr-Abl specific and correlated with known resistance. The results were comparable to those from Western blotting. The method also proved to be reproducible with small samples of normal and Ph(+) CD34(+) cells and was able to discriminate between Ph(-), sensitive and resistant Ph(+) cells. This assay should now enable investigators to unravel the mechanism(s) of IM resistance in stem cells.     

Learning a high-precision locomotor task in patients with Parkinson's disease.

We evaluated the acquisition and performance of a high-precision locomotor task in patients with Parkinson's disease (PD) and healthy subjects. All subjects walked on a treadmill and had to step repetitively as low as possible over an obstacle without touching it. During blocks 1 and 2, the subjects had full vision and received additional acoustic warning and feedback signals. During block 3, vision became restricted. Changes in foot clearance and the number of obstacle hits were evaluated. Initially, PD patients performed poorer and improved foot clearance slower. After task repetition, the groups performed similarly. Restricting vision deteriorated performance in both groups. The similar performance of PD patients after task repetition might indicate that adequate training could improve adaptive locomotor behavior in PD patients.     

Diagnoses of chronic beryllium disease within cohorts of sarcoidosis patients.

An increase in chronic beryllium disease (CBD) has been suggested due to higher industrial use of beryllium alloys. Since occupational CBD is a perfect phenocopy of sarcoidosis, it might be misdiagnosed as sarcoidosis. In the current it was hypothesised that CBD exists in cohorts of sarcoidosis patients. In a prospective case study, sarcoidosis patients were evaluated for potential beryllium exposure. In those patients in whom beryllium exposure was confirmed and beryllium hypersensitivity demonstrated, the diagnosis of sarcoidosis was rejected and corrected to CBD. In 84 patients seen for re-evaluation or making a diagnosis of sarcoidosis, beryllium exposure was recognised and a diagnosis of CBD was made in 34 out of 84 patients. The time lag between clinical diagnosis of sarcoidosis and the final diagnosis of CBD ranged 0-18 yrs (median 3 yrs) and the mean (range) age at time of diagnosis of CBD was 43.9(25-80) yrs. Beryllium-contaminated workplaces causing disease encompassed a wide spectrum of industries and technical trades in which beryllium-exposure is generally not perceived as a health hazard. In conclusion, chronic beryllium disease still belongs to the spectrum of differential diagnoses of granulomatous disorders.     

NT-proBNP reflects right ventricular structure and function in pulmonary hypertension.

The aim of the current study was to investigate whether alterations in N-terminal pro brain natriuretic peptide (NT-proBNP) reflect changes in right ventricular structure and function in pulmonary hypertension patients during treatment. The study consisted of 30 pulmonary hypertension patients; 15 newly diagnosed and 15 on long-term treatment. NT-proBNP, right heart catheterisation and cardiac magnetic resonance imaging measurements were performed, at baseline and follow-up. There were no significant differences between newly diagnosed patients and those on treatment at baseline or follow-up with respect to NT-proBNP, haemodynamics and right ventricular parameters. Relative changes in NT-proBNP during treatment were correlated to the relative changes in right ventricular end-diastolic volume index (r = 0.59), right ventricular mass index (r = 0.62) and right ventricular ejection fraction (r = -0.81). N-terminal pro brain natriuretic peptide measurements reflect changes in magnetic resonance imaging-measured right ventricular structure and function in pulmonary hypertension patients. An increase in N-terminal pro brain natriuretic peptide over time reflects right ventricular dilatation concomitant to hypertrophy and deterioration of systolic function.