Iron excess upregulates SPNS2 mRNA levels but reduces sphingosine-1-phosphate export in human osteoblastic MG-63 cells.

We aimed to study the mechanisms involved in bone-related iron impairment by using the osteoblast-like MG-63 cell line. Our results indicate that iron impact the S1P/S1PR signalizing axis and suggest that iron can affect the S1P process and favor the occurrence of osteoporosis during chronic iron overload. INTRODUCTION: Systemic iron excess favors the development of osteoporosis, especially during genetic hemochromatosis. The cellular mechanisms involved are still unclear despite numerous data supporting a direct effect of iron on bone biology. Therefore, the aim of this study was to characterize mechanisms involved in the iron-related osteoblast impairment. METHODS: We studied, by using the MG-63 cell lines, the effect of iron excess on SPNS2 gene expression which was previously identified by us as potentially iron-regulated. Cell-type specificity was investigated with hepatoma HepG2 and enterocyte-like Caco-2 cell lines as well as in iron-overloaded mouse liver. The SPNS2-associated function was also investigated in MG-63 cells by fluxomic strategy which led us to determinate the S1P efflux in iron excess condition. RESULTS: We showed in MG-63 cells that iron exposure strongly increased the mRNA level of the SPNS2 gene. This was not observed in HepG2, in Caco-2 cells, and in mouse livers. Fluxomic study performed concomitantly on MG-63 cells revealed an unexpected decrease in the cellular capacity to export S1P. Iron excess did not modulate SPHK1, SPHK2, SGPL1, or SGPP1 gene expression, but decreased COL1A1 and S1PR1 mRNA levels, suggesting a functional implication of low extracellular S1P concentration on the S1P/S1PR signalizing axis. CONCLUSIONS: Our results indicate that iron impacts the S1P/S1PR signalizing axis in the MG-63 cell line and suggest that iron can affect the bone-associated S1P pathway and favor the occurrence of osteoporosis during chronic iron overload.

Synthesis and characterization of Ti-27.5Nb alloy made by CLAD® additive manufacturing process for biomedical applications.

Biocompatible beta-titanium alloys such as Ti-27.5(at.%)Nb are good candidates for implantology and arthroplasty applications as their particular mechanical properties, including low Young's modulus, could significantly reduce the stress-shielding phenomenon usually occurring after surgery. The CLAD® process is a powder blown additive manufacturing process that allows the manufacture of patient specific (i.e. custom) implants. Thus, the use of Ti-27.5(at.%)Nb alloy formed by CLAD® process for biomedical applications as a mean to increase cytocompatibility and mechanical biocompatibility was investigated in this study. The microstructural properties of the CLAD-deposited alloy were studied with optical microscopy and electron back-scattered diffraction (EBSD) analysis. The conservation of the mechanical properties of the Ti-27.5Nb material after the transformation steps (ingot-powder atomisation-CLAD) were verified with tensile tests and appear to remain close to those of reference material. Cytocompatibility of the material and subsequent cell viability tests showed that no cytotoxic elements are released in the medium and that viable cells proliferated well.

Fatigue performance evaluation of a Nickel-free titanium-based alloy for biomedical application - Effect of thermomechanical treatments.

In the present work, structural fatigue experiments were performed on a Ti-26Nb alloy subjected to different thermomechanical treatments: a severe cold rolling, a solution treatment and two aging treatments at low-temperature conducted after cold rolling in order to optimize the kinetics of precipitation. The aim is to investigate the effect of microstructural refinement obtained by these processes on fatigue performances. Preliminary tensile tests were performed on each state and analyzed in terms of the microstructure documented by using X-Ray diffraction and TEM analysis. These tests clearly promote the short-time-aged cold-rolled state with a fine α and ω phases precipitation. An interesting balance between mechanical properties such as high strength and low Young's modulus has been obtained. Cyclic bending tests were carried out in air at 0.5%, 1%, 2% and 3% imposed strain amplitudes. At low straining amplitude, where the fatigue performances are at their best, the cold-rolled state does not break at 3×106 cycles and the long-time aged precipitation hardened state seems to be a good competitor compared to the cold-rolled state. All failure characteristics are documented by Scanning Electron Microscopy (SEM) micrographs and analyzed in term of microstructure.

In situ elaboration of a binary Ti-26Nb alloy by selective laser melting of elemental titanium and niobium mixed powders.

Ti-Nb alloys are excellent candidates for biomedical applications such as implantology and joint replacement because of their very low elastic modulus, their excellent biocompatibility and their high strength. A low elastic modulus, close to that of the cortical bone minimizes the stress shielding effect that appears subsequent to the insertion of an implant. The objective of this study is to investigate the microstructural and mechanical properties of a Ti-Nb alloy elaborated by selective laser melting on powder bed of a mixture of Ti and Nb elemental powders (26 at.%). The influence of operating parameters on porosity of manufactured samples and on efficacy of dissolving Nb particles in Ti was studied. The results obtained by optical microscopy, SEM analysis and X-ray microtomography show that the laser energy has a significant effect on the compactness and homogeneity of the manufactured parts. Homogeneous and compact samples were obtained for high energy levels. Microstructure of these samples has been further characterized. Their mechanical properties were assessed by ultrasonic measures and the Young's modulus found is close to that of classically elaborated Ti-26 Nbingot.

[Phalloidin syndrome: role of Elisa-based assay for the detection of alpha- and gamma-amanitins in urine. Preliminary results]. / Syndrome phalloïdien: quelle est la place du dosage des alpha- et gamma-amanitines par ELISA (Bühlmann)? Résultats préliminaires.

UNLABELLED: After consumption of mushrooms containing amatoxins (Amanita, Lepiota, and Galerina species), symptoms usually develop after a long delay (>6 h). Initial symptoms start as severe gastroenteritis, progressing to liver failure and possibly death as a result of hepatic coma. Since the survival rate of poisoned patients is claimed to depend on the time of beginning of efficient treatment, fast and reliable assays for amatoxins in biological fluids are essential. Described analytical methods for amatoxins include high performance liquid chromatography and radioimmunoassay (RIA). Recently, a new enzyme-linked immunosorbent assay (Bühlmann Amanitin ELISA kit) has been introduced as an alternative method to RIA. This ELISA-based assay offers several advantages: no complex extraction procedure is required (vs. HPLC) and no safety precautions concerning radioactivity have to be taken (vs. RIA). From August 2004 to October 2005, a pilot study was performed to test the practicability and the clinical utility of this method in emergency situations. RESULTS: ten urines, 9 serums and 1 faeces from 10 patients suffering from acute gastroenteritis after mushroom ingestions (7 contaminated meals) were analyzed. Definitive diagnosis of amatoxin poisoning was made in 4 cases (3 contaminated meals) on the basis of the anamnesis, laboratory results, and clinical course. A patient developed a severe amatoxin poisoning with urinary amanitins level < 1.5 microg/L (urines were collected more than 72 h after mushroom ingestion). Two patients were paucisymptomatic with urinary amanitins levels >10 microg/L (urines were collected before the 36th hour). CONCLUSION: Urine is the sample of choice for the determination of amatoxins. The most critical factor to invalidate the usefulness of this analysis is time. After 36 h, the sensitivity is unreliable.

How many members must an orthopaedic department have to teach effectively?

Although the subject matter contained in the curriculum of a medical school has expanded continuously, the time to present this material to the students has diminished. With the abandonment of most lectures in clinical subjects, students have been exposed to the surgical specialties by short required rotations through the services. Often these rotations are offered only as electives. However, the surgical specialties such as orthopaedic surgery have increased considerably in subject matter and scope. It no longer is possible to present the subject in a series of 10 or 12 lectures given by full-time or part-time faculty. Instead, to showcase the subject of orthopaedic surgery requires a clinical service that contains the full spectrum of the specialty from athletic injuries to scoliosis. Only in this way can the specialty attract the bright and capable students who will become the leaders of orthopaedics in the future. To field such a panoply of specialists requires a combined effort by the school, the hospital, and the private sector.

Patron saints of medicine.

From the earliest times, medical practitioners have sought divine help and support to aid them as they go about their busy rounds. In the early Christian era, 4 individuals were singled out as patron saints of medicine, and particularly of physicians and surgeons. These men were all natives of Asia Minor; they were all educated in the Greek medical tradition; and they were all busy practitioners. They were the Apostle Luke, Saints Cosmas and Damian and Saint Panteleimon. Through the centuries, they have served as worthy role models for the physicians who have invoked their aide.

Useful hints for the study of the history of orthopaedics.

Although there is considerable interest among orthopaedic surgeons in the history of their specialty, many fail to pursue their interest because of an unfamiliarity with the tools and methods by which historical information can be assembled. The purpose of this article is to point out the resources for historical research available to most physicians and to give some suggestions for their use.

Fat embolism. A perspective.

The importance of fat embolism as a complication of bony trauma has been recognized for over 100 years. During this time there have been short bursts of rapid progress in knowledge and understanding of the problem separated by periods of confusion and misunderstandings. Presently, as a result of improvements in technology, new information has been derived to reduce significantly the morbidity and mortality of fat embolism.

Naproxen tolerability in the elderly: a summary report.

Naproxen tolerability in elderly patients was assessed using data from 9 double blind clinical trials. We analyzed the percentage of patients who (a) withdrew for complaints, (b) reported complaints, and (c) exhibited clinically significant laboratory test abnormalities. Among 1,178 patients with rheumatoid arthritis or osteoarthritis, 26% were 65 years old or older. These elderly patients demonstrated no consistent decrease in tolerability, or increase in toxicity, of naproxen, as compared with younger patients.

Effect of fenprostalene, a PGF(2)alpha analogue, on plasma levels of estradiol-17beta and progesterone in cyclic heifers.

Following a 40-day acclimatization period, 12 cyclic beef heifers entered a 95- to 101-day test period. Prior to fenprostalene treatment, all animals were studied through two normal estrous cycles. Plasma samples were obtained daily from all animals during the course of the study and were assayed for estradiol-17beta and progesterone. Group 1 heifers (n=6) were then treated with fenprostalene at mid-cycle during two subsequent cycles. This treatment was accomplished by treating the animals 11 days after the first clinically observed signs of estrus following Study Day 21 and treating them again 11 days later. Each treatment consisted of a subcutaneous injection of 1.0 mg fenprostalene. The animals were studied through two or three estrous cycles following the second injection. The Group 2 animals (n=6) were maintained as untreated controls through a corresponding period. Fenprostalene induced estrus in five of six treated heifers within 5 d following the first injection and in five of six heifers within 3 d following the second injection. The mean time to estrus was 3.4 d (+/- 1.1 d SD) following the first injection and 2.2 d (+/-0.8 days SD) following the second injection. No significant differences were found in the plasma levels of estradiol-17beta and progesterone when comparing fenprostalene-induced cycles to those that occurred naturally. The fenprostalene injection reset the estrous cycle without changing the nature of the cycle. The time of clinically detected estrus usually coincided with a sharp peak in estradiol-17beta concentration.